Difference between revisions of "Staging page"

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{{#lst:Section editor transclusions|breast}}
 
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<big>'''Note: these are regimens tested in biomarker-specific populations, please see the [[breast cancer|main breast cancer page]] for other regimens.'''</big>
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
−
==[https://www.asco.org/ ASCO]==
 
−
*'''2022:''' Andre et al. [https://doi.org/10.1200/jco.22.00069 Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update]
 
−
*'''2022:''' Giordano et al. [https://doi.org/10.1200/jco.21.02677 Abemaciclib With Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update]
 
−
*'''2021:''' Korde et al. [https://doi.org/10.1200/jco.20.03399 Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline]
 
−
*'''2019:''' Burstein et al. [https://doi.org/10.1200/JCO.18.01160 Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: ASCO Clinical Practice Guideline focused update]
 
−
===Older===
 
−
*'''2016:''' Burstein et al. [https://doi.org/10.1200/JCO.2015.65.9573 Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline update on ovarian suppression] [https://pubmed.ncbi.nlm.nih.gov/26884856 PubMed]
 
−
*'''2016:''' Rugo et al. [https://doi.org/10.1200/JCO.2016.67.1487 Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline] [https://pubmed.ncbi.nlm.nih.gov/27217461 PubMed]
 
−
*'''2016:''' Harris et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933134/ Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline]
 
−
*'''2015:''' Van Poznak et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478102/ Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline]
 
−
*'''2014:''' Burstein et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876310/ Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline focused update]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf NCCN Guidelines - Breast Cancer]
 
−
== St Gallen Breast Guidelines ==
 
−
*'''2019:''' Burstein et al. [https://academic.oup.com/annonc/article/30/10/1541/5543097 Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019]
 
−
===Older===
 
−
*'''2017:''' Curigliano et al. [https://pubmed.ncbi.nlm.nih.gov/28838210 St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017]
 
−
*'''2015:''' Coates et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511219/ Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015]
 
−
=Neoadjuvant endocrine therapy, premenopausal=
 
−
==Anastrozole & Goserelin {{#subobject:6e3249|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a131ba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70373-4 Masuda et al. 2012 (STAGE)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Goserelin_.26_Tamoxifen|Goserelin & Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior RR
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once per month
 
−
'''24-week course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# '''STAGE:''' Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. [https://doi.org/10.1016/S1470-2045(11)70373-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22265697 PubMed] NCT00605267
 
−
==Anastrozole, Goserelin, Palbociclib {{#subobject:6e3ug7|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1ug7zba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555232/ Ma et al. 2017 (NeoPalAna)]
 
−
|2013-2015
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Goserelin (Zoladex)]] 3.6 mg IM once on day 1
 
−
====Targeted therapy====
 
−
*[[Palbociclib (Ibrance)]] as follows:
 
−
**Cycles 2 to 5: 125 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 5 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# '''NeoPalAna:''' Ma CX, Gao F, Luo J, Northfelt DW, Goetz M, Forero A, Hoog J, Naughton M, Ademuyiwa F, Suresh R, Anderson KS, Margenthaler J, Aft R, Hobday T, Moynihan T, Gillanders W, Cyr A, Eberlein TJ, Hieken T, Krontiras H, Guo Z, Lee MV, Spies NC, Skidmore ZL, Griffith OL, Griffith M, Thomas S, Bumb C, Vij K, Bartlett CH, Koehler M, Al-Kateb H, Sanati S, Ellis MJ. NeoPalAna: neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor-positive breast cancer. Clin Cancer Res. 2017 Aug 1;23(15):4055-4065. Epub 2017 Mar 7. [https://clincancerres.aacrjournals.org/content/23/15/4055.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555232/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28270497 PubMed] NCT01723774
 
−
==Goserelin & Tamoxifen {{#subobject:23ef1e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:833f0d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70373-4 Masuda et al. 2012 (STAGE)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_.26_Goserelin|Anastrozole & Goserelin]]
 
−
| style="background-color:#d73027" |Inferior RR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7251809/ Kim et al. 2020 (NEST)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer#AC-D|AC-D]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior clinical response
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once per month
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''24-week course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# '''STAGE:''' Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. [https://doi.org/10.1016/S1470-2045(11)70373-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22265697 PubMed] NCT00605267
 
−
# '''NEST:''' Kim HJ, Noh WC, Lee ES, Jung YS, Kim LS, Han W, Nam SJ, Gong GY, Kim HJ, Ahn SH. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer. Breast Cancer Res. 2020 May 27;22(1):54. [https://doi.org/10.1186/s13058-020-01288-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7251809/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32460816/ PubMed] NCT01622361
 
−
=Neoadjuvant endocrine therapy, postmenopausal=
 
−
==Anastrozole monotherapy {{#subobject:f8140f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3-month course {{#subobject:fbebb0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.04.005 Smith et al. 2005 (IMPACT)]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Anastrozole_.26_Tamoxifen_99|Anastrozole & Tamoxifen]]<br> 2. [[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.21872 Cataliotti et al. 2006 (PROACT)]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.22789 Semiglazov et al. 2007]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ooc)
 
−
|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_88|Doxorubicin & Paclitaxel (AT)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: while Semiglazov et al. 2007 is a technically negative study, it is one of very few that directly compare endocrine therapy to chemotherapy.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''12-week course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4-month course {{#subobject:84024b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ Ellis et al. 2011 (ACOSOG Z1031)]
 
−
|2006-2009
 
−
| style="background-color:#91cf61" |Screening Phase II
 
−
|cRR: 69% (95% CI, 60-77)
 
−
|-
 
−
|}
 
−
''Note: ACOSOG Z1031 was randomized but with the intent to select candidates for phase III trials; efficacy comparisons were not made.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''16- to 18-week course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# '''IMPACT:''' Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, Ashley SE, Francis S, Boeddinghaus I, Walsh G; IMPACT Trialists Group. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005 Aug 1;23(22):5108-16. Epub 2005 Jul 5. [https://doi.org/10.1200/JCO.2005.04.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15998903 PubMed]
 
−
# '''PROACT:''' Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, Dube P, de Oliveira CT. Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial. Cancer. 2006 May 15;106(10):2095-103. [https://doi.org/full/10.1002/cncr.21872 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16598749 PubMed] NCT00232661
 
−
#Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007 Jul 15;110(2):244-54. [https://doi.org/10.1002/cncr.22789 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17538978/ PubMed]
 
−
# '''ACOSOG Z1031:''' Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. Epub 2011 May 9. [https://doi.org/10.1200/JCO.2010.31.6950 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21555689 PubMed] NCT00265759
 
−
# '''Meta-analysis:''' Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. [https://doi.org/10.1001/jamaoncol.2016.1897 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5738656/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27367583/ PubMed]
 
−
#'''POETIC:''' Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. [https://doi.org/10.1016/s1470-2045(20)30458-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7606901/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33152284 PubMed] NCT02338310
 
−
# '''Alliance A011106:''' NCT01953588
 
−
==Anastrozole & Palbociclib {{#subobject:6e3249|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a131ba|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555232/ Ma et al. 2017 (NeoPalAna)]
 
−
|2013-2015
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Palbociclib (Ibrance)]] as follows:
 
−
**Cycles 2 to 5: 125 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 5 cycles'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# '''NeoPalAna:''' Ma CX, Gao F, Luo J, Northfelt DW, Goetz M, Forero A, Hoog J, Naughton M, Ademuyiwa F, Suresh R, Anderson KS, Margenthaler J, Aft R, Hobday T, Moynihan T, Gillanders W, Cyr A, Eberlein TJ, Hieken T, Krontiras H, Guo Z, Lee MV, Spies NC, Skidmore ZL, Griffith OL, Griffith M, Thomas S, Bumb C, Vij K, Bartlett CH, Koehler M, Al-Kateb H, Sanati S, Ellis MJ. NeoPalAna: neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor-positive breast cancer. Clin Cancer Res. 2017 Aug 1;23(15):4055-4065. Epub 2017 Mar 7. [https://clincancerres.aacrjournals.org/content/23/15/4055.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555232/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28270497 PubMed] NCT01723774
 
−
==Exemestane monotherapy {{#subobject:62jxx3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:12d98q|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.22789 Semiglazov et al. 2007]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ooc)
 
−
|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_88|Doxorubicin & Paclitaxel (AT)]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: while this is a technically negative study, it is one of very few that directly compare endocrine therapy to chemotherapy.''
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''3-month course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
#Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007 Jul 15;110(2):244-54. [https://doi.org/10.1002/cncr.22789 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17538978/ PubMed]
 
−
# '''Meta-analysis:''' Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. [https://doi.org/10.1001/jamaoncol.2016.1897 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5738656/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27367583/ PubMed]
 
−
==Letrozole monotherapy {{#subobject:c68c77|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c83e5c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.18.3808 Ellis et al. 2001]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1023/a:1013128213451 Eiermann et al. 2001 (P024)]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ Ellis et al. 2011 (ACOSOG Z1031)]
 
−
|2006-2009
 
−
| style="background-color:#91cf61" |Screening Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
|cRR: 75% (95% CI, 66-82)
 
−
|-
 
−
|}
 
−
''Note: ACOSOG Z1031 gave a total treatment duration of 16 to 18 weeks, which is approximately 4 months. Also, this trial was randomized but with the intent to select candidates for phase III trials; efficacy comparisons were not made.''
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''4-month course'''
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Jänicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol. 2001 Sep 15;19(18):3808-16. [https://doi.org/10.1200/JCO.2001.19.18.3808 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11559718 PubMed]
 
−
# '''P024:''' Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA, Dugan M, Borgs M, Semiglazov V; Letrozole Neo-Adjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol. 2001 Nov;12(11):1527-32. [https://doi.org/10.1023/a:1013128213451 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11822750 PubMed]
 
−
# '''ACOSOG Z1031:''' Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. Epub 2011 May 9. [https://doi.org/10.1200/JCO.2010.31.6950 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21555689 PubMed] NCT00265759
 
−
# '''Meta-analysis:''' Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. [https://doi.org/10.1001/jamaoncol.2016.1897 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5738656/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27367583/ PubMed]
 
−
#'''POETIC:''' Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. [https://doi.org/10.1016/s1470-2045(20)30458-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7606901/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33152284 PubMed] NCT02338310
 
−
=Neoadjuvant response criteria=
 
−
==Clinical response rate (cRR)==
 
−
''Although fairly dated, some trials such as [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ ACOSOG Z1031] make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.''
 
−
</div></div>
 
−
===References===
 
−
# Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. [https://doi.org/10.1002/1097-0142(19810101)47:1%3C207::AID-CNCR2820470134%3E3.0.CO;2-6 link to original article]  [https://pubmed.ncbi.nlm.nih.gov/7459811 PubMed]
 
−
==Miller-Payne scoring system==
 
−
*Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
 
−
*Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
 
−
*Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
 
−
*Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
 
−
*Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma ''in situ'' may be present)
 
−
</div></div>
 
−
===References===
 
−
# Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. [http://www.thebreastonline.com/article/S0960-9776(03)00106-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14659147 PubMed]
 
−
==Residual cancer burden (RCB)==
 
−
*The RCB is calculated as follows: RCB = 1.4 (''f<sub>inv</sub>*d<sub>prim</sub>'')<sup>0.17</sup> + [4(1 - 0.75<sup>''LN''</sup>)''d<sub>met</sub>'']<sup>0.17</sup>
 
−
**where ''d<sub>prim</sub>'' is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, ''f<sub>inv</sub>'' is the proportion of the primary tumor bed that contains invasive carcinoma, ''LN'' is the number of axillary lymph nodes containing metastatic carcinoma, and ''d<sub>met</sub>'' is the diameter of the largest metastasis in an axillary lymph node.
 
−
**The cut-off points are 1.36 and 3.28.
 
−
</div></div>
 
−
===References===
 
−
# Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. [https://doi.org/10.1200/JCO.2007.10.6823 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17785706 PubMed]
 
−
==Residual disease in breast and nodes (RDBN)==
 
−
*Level 1: pCR in breast and nodes with or without ''in situ'' carcinoma
 
−
*Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
 
−
</div></div>
 
−
===References===
 
−
# Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. [https://insights.ovid.com/pubmed?pmid=18391619 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18391619 PubMed]
 
−
==Sataloff's classification==
 
−
*Breast:
 
−
**T-A: Total or nearly total therapeutic effect
 
−
**T-B: Greater than 50% therapeutic effect
 
−
**T-C: Less than 50% therapeutic effect
 
−
**T-D: No therapeutic effect
 
−
*Lymph node:
 
−
**N-A: Therapeutic effect but no metastasis
 
−
**N-B: No metastasis, no therapeutic effect
 
−
**N-C: Therapeutic effect but metastasis
 
−
**N-D: Metastasis, no therapeutic effect
 
−
</div></div>
 
−
===References===
 
−
# Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. [https://pubmed.ncbi.nlm.nih.gov/7874340 PubMed]
 
−
==Tumor response ratio==
 
−
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
 
−
*TRR = 0: pathologic complete response (pCR)
 
−
*TRR greater than 0 up to 0.4: strong partial response
 
−
*TRR greater than 0.4 up to 1.0: weak partial response (WPR)
 
−
*TRR greater than 1.0: tumor growth
 
−
</div></div>
 
−
===References===
 
−
# Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. [https://link.springer.com/article/10.1245/s10434-014-3922-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25059788 PubMed]
 
−
==ypTNM staging==
 
−
This system is proprietary to the AJCC. Please [https://cancerstaging.org/Pages/default.aspx visit their site] or consult the AJCC Manual for further details.
 
−
=Adjuvant therapy, premenopausal=
 
−
==Exemestane & OFS {{#subobject:ajhg71|Regimen=1}}==
 
−
Exemestane & OFS: Exemestane & '''<u>O</u>'''varian '''<u>F</u>'''unction '''<u>S</u>'''uppression
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:818d9f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (TEXT)]
 
−
|rowspan="2"|2003-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy|Tamoxifen & OFS]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (SOFT)]
 
−
|rowspan="2"|2003-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy|Tamoxifen & OFS]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|}
 
−
''Note: Pagani et al. 2014 report on two trials, but only SOFT had the tamoxifen only arm.''
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
*Ovarian function suppression by the following study-specific criteria:
 
−
**TEXT: [[Triptorelin (Trelstar LA)]] 3.75 mg IM once on day 1
 
−
***"[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]] or [[Endocrine_ablation_surgery#Ovarian_irradiation|ovarian irradiation]] was allowed after at least 6 months of triptorelin."
 
−
**SOFT: Choice of mechanism left to investigators
 
−
'''28-day cycle for 65 cycles (5 years)'''
 
−
</div></div>
 
−
===References===
 
−
# '''TEXT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [https://doi.org/10.1056/NEJMoa1404037 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881463 PubMed] NCT00066703
 
−
## '''Pooled update:''' Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Láng I, Gómez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. Epub 2019 Oct 16. [https://doi.org/10.1200/jco.18.01967 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7164485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31618131 PubMed]
 
−
# '''SOFT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [https://doi.org/10.1056/NEJMoa1404037 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881463 PubMed] NCT00066690
 
−
## '''Update:''' Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. [https://doi.org/10.1056/NEJMoa1412379 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25495490 PubMed]
 
−
## '''Pooled update:''' Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Láng I, Gómez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. Epub 2019 Oct 16. [https://doi.org/10.1200/jco.18.01967 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7164485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31618131 PubMed]
 
−
==Goserelin monotherapy {{#subobject:42a67a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:eefa6c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.551 Davidson et al. 2005 (ECOG E5188)]
 
−
|1989-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Goserelin_.26_Tamoxifen_2|Goserelin & Tamoxifen]] x 5 y
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.05.042 Jonat et al. 2002 (ZEBRA)]
 
−
|1990-1996
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#eeee01" |Equivalent DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*ECOG E5188 & ZEBRA: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once on day 1
 
−
'''28-day cycle for 26 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
# '''ZEBRA:''' Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M, Lisboa B; Zoladex Early Breast Cancer Research Association Study. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: the Zoladex Early Breast Cancer Research Association study. J Clin Oncol. 2002 Dec 15;20(24):4628-35. [https://doi.org/10.1200/JCO.2002.05.042 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488406 PubMed]
 
−
# '''ECOG E5188:''' Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, Abeloff MD. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005 Sep 1;23(25):5973-82. Epub 2005 Aug 8. [https://doi.org/10.1200/JCO.2005.05.551 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16087950 PubMed]
 
−
==Goserelin & Tamoxifen {{#subobject:23ef1e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:833f0d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.05.551 Davidson et al. 2005 (ECOG E5188)]
 
−
|1989-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Goserelin_monotherapy|Goserelin]] x 5 y
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.09.112 Jakesz et al. 2002 (ABCSG 5)]
 
−
|1990-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*ABCSG 5: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
*ECOG E5188: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg IM depot once per month
 
−
**Note: ABCSG 5 stopped goserelin after 3 years
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''5-year course (see note)'''
 
−
</div></div>
 
−
===References===
 
−
# '''ABCSG 5:''' Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T, Seifert M, Haider K, Mlineritsch B, Steindorfer P, Kwasny W, Fridrik M, Steger G, Wette V, Samonigg H; ABCSG. Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5. J Clin Oncol. 2002 Dec 15;20(24):4621-7. [https://doi.org/10.1200/JCO.2002.09.112 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12488405 PubMed] NCT00309478
 
−
# '''ECOG E5188:''' Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, Abeloff MD. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol. 2005 Sep 1;23(25):5973-82. Epub 2005 Aug 8. [https://doi.org/10.1200/JCO.2005.05.551 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16087950 PubMed]
 
−
==Leuprolide monotherapy {{#subobject:714c67|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bf0009|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.8534 Schmid et al. 2007 (TABLE)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Leuprolide (Lupron)]] 11.25 mg SC once on day 1
 
−
'''3-month cycle for 8 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002; the San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003; the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004; and the San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004. -->
 
−
# '''TABLE:''' Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, Lehmann U, Maubach L, Meurer J, Wallwiener D, Possinger K. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. J Clin Oncol. 2007 Jun 20;25(18):2509-15. [https://doi.org/10.1200/jco.2006.08.8534 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17577027 PubMed]
 
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==Tamoxifen monotherapy {{#subobject:ughab1|Regimen=1}}==
 
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<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2 years of 20 mg/day {{#subobject:bb9926|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(04)00565-9 Rydén et al. 2005 (SBII:2pre)]
 
−
|1986-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''2-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5 years {{#subobject:dcjgu3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1093/jnci/djk109 Adjuvant Breast Cancer Trials Collaborative Group 2007 (NCRI ABC-OAS)]
 
−
|1992-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_OFS|Tamoxifen & OFS]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RFS/OS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2813306/ Bramwell et al. 2009 (NCIC-CTG MA.12)]
 
−
|1993-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>OS60: 87% vs 82%<br>(HR 0.78, 95% CI 0.57-1.06)
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251958/ Tevaarwerk et al. 2014 (ECOG E-3193)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_OFS|Tamoxifen & OFS]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
| style="background-color:#1a9850" |Fewer menopausal symptoms
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (SOFT)]
 
−
|rowspan=2|2003-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Exemestane_monotherapy_2|Exemestane & OFS]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|
 
−
|-
 
−
|2. [[#Tamoxifen_.26_OFS|Tamoxifen & OFS]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.00126 Kim et al. 2019 (ASTRRA)]
 
−
|2009-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_OFS|Tamoxifen & OFS]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>2</sup>
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Pagani et al. 2014 reports on two trials, but only SOFT had the tamoxifen only arm; efficacy for this arm is as reported in Francis et al. 2015.''<br>
 
−
''<sup>2</sup>In an abstract-only update, overall survival was not significantly different in longer follow-up; awaiting publication of this update.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day or 10 mg PO twice per day (the latter dosing is typical in older trials only)
 
−
'''5-year course'''
 
−
</div></div>
 
−
===References===
 
−
# '''SBII:2pre:''' Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. [https://www.ejcancer.com/article/S0959-8049(04)00565-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15661551 PubMed]
 
−
## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [https://doi.org/10.1200/jco.2015.65.6272 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27161974 PubMed]
 
−
## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L; South Swedish and South-East Swedish Breast Cancer Groups. Effects of adjuvant tamoxifen over three decades on breast cancer-free and distant recurrence-free interval among premenopausal women with oestrogen receptor-positive breast cancer randomised in the Swedish SBII:2pre trial. Eur J Cancer. 2019 Mar;110:53-61. Epub 2019 Feb 12. [https://doi.org/10.1016/j.ejca.2018.12.034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30769227 PubMed]
 
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# '''IBCSG 13-93:''' Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. [https://doi.org/10.1200/JCO.2005.03.0783 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16505417 PubMed]
 
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# '''NCRI ABC-OAS:''' Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. J Natl Cancer Inst. 2007 Apr 4;99(7):516-25. [https://doi.org/10.1093/jnci/djk109 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17405996/ PubMed] NCT00002582
 
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# '''NCIC-CTG MA.12:''' Bramwell VHC, Pritchard KI, Tu D, Tonkin K, Vachhrajani H, Vandenberg TA, Robert J, Arnold A, O'Reilly SE, Graham B, Shepherd L. A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada--Clinical Trials Group Trial, MA.12). Ann Oncol. 2010 Feb;21(2):283-290. Epub 2009 Jul 23. [https://doi.org/10.1093/annonc/mdp326 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2813306/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19628570/ PubMed] NCT00002542
 
−
# '''SOFT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [https://doi.org/10.1056/NEJMoa1404037 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881463 PubMed] NCT00066690
 
−
## '''Update:''' Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. [https://doi.org/10.1056/NEJMoa1412379 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25495490 PubMed]
 
−
## '''Pooled update:''' Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Láng I, Gómez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. Epub 2019 Oct 16. [https://doi.org/10.1200/jco.18.01967 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7164485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31618131 PubMed]
 
−
# '''ECOG E-3193:''' Tevaarwerk AJ, Wang M, Zhao F, Fetting JH, Cella D, Wagner LI, Martino S, Ingle JN, Sparano JA, Solin LJ, Wood WC, Robert NJ. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014 Dec 10;32(35):3948-58. Epub 2014 Oct 27. [https://doi.org/10.1200/JCO.2014.55.6993 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251958/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25349302 PubMed]
 
−
# '''ASTRRA:''' Kim HA, Lee JW, Nam SJ, Park BW, Im SA, Lee ES, Jung YS, Yoon JH, Kang SS, Lee SJ, Park KH, Jeong J, Cho SH, Kim SY, Kim LS, Moon BI, Lee MH, Kim TH, Park C, Jung SH, Gwak G, Kim J, Kang SH, Jin YW, Kim HJ, Han SH, Han W, Hur MH, Noh WC; Korean Breast Cancer Study Group. Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial. J Clin Oncol. 2020 Feb 10;38(5):434-443. Epub 2019 Sep 16. [https://doi.org/10.1200/jco.19.00126 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31518174/ PubMed] NCT00912548
 
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==Tamoxifen & OFS {{#subobject:97a16d|Regimen=1}}==
 
−
Tamoxifen & OFS: Tamoxifen & OFS: '''<u>O</u>'''varian '''<u>F</u>'''unction '''<u>S</u>'''uppression
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3 years {{#subobject:de0411|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0806285 Gnant et al. 2009 (ABCSG-12)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen.2C_OFS.2C_Zoledronic_acid_88|Tamoxifen, OFS, Zoledronic acid]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
'''28-day cycle for 39 cycles (3 years)'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5 years {{#subobject:4656a6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251958/ Tevaarwerk et al. 2014 (ECOG E-3193)]
 
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
| style="background-color:#d73027" |More menopausal symptoms
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (TEXT)]
 
−
|rowspan="2"|2003-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Exemestane_monotherapy_2|Exemestane & OFS]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup>
 
−
|
 
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ Pagani et al. 2014 (SOFT)]
 
−
|rowspan="2"|2003-2011
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Exemestane_monotherapy_2|Exemestane & OFS]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup>
 
−
|
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/j.ejca.2019.05.004 Perrone et al. 2019 (HOBOE)]
 
−
|rowspan="2"|2004-2015
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Letrozole_.26_OFS_88|Letrozole & OFS]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
|
 
−
|-
 
−
|2. [[#Zoledronic_acid_.26_OFS_88|ZL & OFS]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
| style="background-color:#1a9850" |Better tolerated
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.00126 Kim et al. 2019 (ASTRRA)]
 
−
|2009-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>2</sup><br>OS60: 99.4% vs 97.8%<br>(HR 0.31, 95% CI 0.10-0.94)
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Pagani et al. 2014 reports on two trials, but only SOFT had the tamoxifen only arm; efficacy for this arm is as reported in Francis et al. 2015.''<br>
 
−
''<sup>2</sup>In an abstract-only update, overall survival was not significantly different in longer follow-up; awaiting publication of this update.''<br>
 
−
''Note: These regimens are intended for premenopausal patients. Patients in HOBOE stopped triptorelin if they reached 55 years of age.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
*Ovarian function suppression by the following study-specific criteria:
 
−
**TEXT: [[Triptorelin (Trelstar LA)]] 3.75 mg IM once on day 1
 
−
***"[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]] or [[Endocrine_ablation_surgery#Ovarian_irradiation|ovarian irradiation]] was allowed after at least 6 months of triptorelin."
 
−
**SOFT: Choice of mechanism left to investigators
 
−
**HOBOE: [[Triptorelin (Trelstar LA)]] 3.75 mg IM once on day 1
 
−
**ASTRRA: [[Goserelin (Zoladex)]] as follows:
 
−
***Cycles 1 to 26: 3.6 mg SC once on day 1
 
−
'''28-day cycle for 65 cycles (5 years)'''
 
−
</div></div>
 
−
===References===
 
−
# '''ABCSG-12:''' Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Marth C, Greil R; ABCSG. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009 Feb 12;360(7):679-91. Erratum in: N Engl J Med. 2009 May 28;360(22):2379. [https://doi.org/10.1056/NEJMoa0806285 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19213681 PubMed] NCT00295646
 
−
## '''Update:''' Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, Greil R; ABCSG. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011 Jul;12(7):631-41. Epub 2011 Jun 5. [https://doi.org/10.1016/S1470-2045(11)70122-X linkt o original article] [https://pubmed.ncbi.nlm.nih.gov/21641868 PubMed]
 
−
# '''SOFT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [https://doi.org/10.1056/NEJMoa1404037 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881463 PubMed] NCT00066690
 
−
## '''Update:''' Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. [https://doi.org/10.1056/NEJMoa1412379 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25495490 PubMed]
 
−
## '''Pooled update:''' Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Láng I, Gómez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. Epub 2019 Oct 16. [https://doi.org/10.1200/jco.18.01967 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7164485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31618131 PubMed]
 
−
# '''TEXT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [https://doi.org/10.1056/NEJMoa1404037 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881463 PubMed] NCT00066703
 
−
## '''Pooled update:''' Pagani O, Francis PA, Fleming GF, Walley BA, Viale G, Colleoni M, Láng I, Gómez HL, Tondini C, Pinotti G, Di Leo A, Coates AS, Goldhirsch A, Gelber RD, Regan MM; SOFT and TEXT Investigators and International Breast Cancer Study Group. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol. 2020 Apr 20;38(12):1293-1303. Epub 2019 Oct 16. [https://doi.org/10.1200/jco.18.01967 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7164485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31618131 PubMed]
 
−
# '''ECOG E-3193:''' Tevaarwerk AJ, Wang M, Zhao F, Fetting JH, Cella D, Wagner LI, Martino S, Ingle JN, Sparano JA, Solin LJ, Wood WC, Robert NJ. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014 Dec 10;32(35):3948-58. Epub 2014 Oct 27. [https://doi.org/10.1200/JCO.2014.55.6993 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251958/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25349302 PubMed]
 
−
# '''HOBOE:''' Perrone F, De Laurentiis M, De Placido S, Orditura M, Cinieri S, Riccardi F, Ribecco AS, Putzu C, Del Mastro L, Rossi E, Tinessa V, Mosconi AM, Nuzzo F, Di Rella F, Gravina A, Iodice G, Landi G, Pacilio C, Forestieri V, Lauria R, Fabbri A, Ibrahim T, De Maio E, Barni S, Gori S, Simeon V, Arenare L, Daniele G, Piccirillo MC, Normanno N, de Matteis A, Gallo C. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial. Eur J Cancer. 2019 Sep;118:178-186. Epub 2019 Jun 1. [https://doi.org/10.1016/j.ejca.2019.05.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31164265 PubMed] NCT00412022
 
−
# '''ASTRRA:''' Kim HA, Lee JW, Nam SJ, Park BW, Im SA, Lee ES, Jung YS, Yoon JH, Kang SS, Lee SJ, Park KH, Jeong J, Cho SH, Kim SY, Kim LS, Moon BI, Lee MH, Kim TH, Park C, Jung SH, Gwak G, Kim J, Kang SH, Jin YW, Kim HJ, Han SH, Han W, Hur MH, Noh WC; Korean Breast Cancer Study Group. Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial. J Clin Oncol. 2020 Feb 10;38(5):434-443. Epub 2019 Sep 16. [https://doi.org/10.1200/jco.19.00126 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31518174/ PubMed] NCT00912548
 
−
=Adjuvant therapy=
 
−
==Abemaciclib & ET {{#subobject:ajgu14|Regimen=1}}==
 
−
Abemaciclib & ET: Abemaciclib & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:41c2e3|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339/ Johnston et al. 2020 (monarchE)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|Endocrine therapy
 
−
| style="background-color:#1a9850" |Superior IDFS<sup>1</sup><br>IDFS36: 88.8% vs 83.4%<br>(HR 0.70, 95% CI 0.59-0.82)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 
−
''Note: the type and dosage of endocrine therapy was not specified in the protocol and was left to clinician discretion.''
 
−
====Targeted therapy====
 
−
*[[Abemaciclib (Verzenio)]] 150 mg PO twice per day
 
−
'''2-year course'''
 
−
====Endocrine therapy====
 
−
*[[:Category:Antiestrogens|Endocrine therapy]] (clinician choice)
 
−
'''5- to 10-year course'''
 
−
</div></div>
 
−
===References===
 
−
#'''monarchE:''' Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortés J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. Epub 2020 Sep 20. [https://doi.org/10.1200/jco.20.02514 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32954927 PubMed] NCT03155997
 
−
##'''Update:''' Harbeck N, Rastogi P, Martin M, Tolaney SM, Shao ZM, Fasching PA, Huang CS, Jaliffe GG, Tryakin A, Goetz MP, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Del Mastro L, Steger GG, Kreipe H, Hegg R, Sohn J, Guarneri V, Cortés J, Hamilton E, André V, Wei R, Barriga S, Sherwood S, Forrester T, Munoz M, Shahir A, San Antonio B, Nabinger SC, Toi M, Johnston SRD, O'Shaughnessy J; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021 Dec;32(12):1571-1581. Epub 2021 Oct 14. [https://doi.org/10.1016/j.annonc.2021.09.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34656740/ PubMed]
 
−
==Anastrozole monotherapy {{#subobject:a052f4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3-year course {{#subobject:41c2e3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ARNO 95)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#ARNO_95|See link]]
 
−
| style="background-color:#91cf60" |[[Complex_multipart_regimens#ARNO_95|See link]]
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ABCSG-8)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#ABCSG-8|See link]]
 
−
| style="background-color:#d9ef8b" |[[Complex_multipart_regimens#ABCSG-8|See link]]
 
−
|
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/99/24/1845/2522241 Jakesz et al. 2007 (ABCSG-6a)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|No further treatment]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30600-9 Tjan-Heijnen et al. 2017 (DATA)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_2|Anastrozole]] x 6 y
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
| style="background-color:#1a9851" |Less toxic
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
|
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*ABCSG-8, ARNO 95, FATA-GIM3: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
*ABCSG-6a: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y versus [[#Aminoglutethemide_.26_Tamoxifen_99|Aminoglutethemide & Tamoxifen]] x 5 y
 
−
*DATA: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3 y
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''3-year course, for a total of 5 to 8 years of hormonal therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 5-year course {{#subobject:b05e8a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S0140-6736(02)09088-8 Baum et al. 2002 (ATAC)]
 
−
| rowspan = "2"|1996-2000
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|1. [[#Anastrozole_.26_Tamoxifen_99|Anastrozole & Tamoxifen]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior DFS<sup>1</sup><br>RFS120: 80.3% vs 76%<br>(HR 0.86, 95% CI 0.78-0.95)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ Goss et al. 2013 (NCIC-CTG MA.27)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_monotherapy_2|Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS60
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.2871 Smith et al. 2017 (FACE)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y, then AI x 3 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-019-05296-8 Ruíz-Borrego et al. 2019 (GEICAM/2006-10)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_.26_Fulvestant_99|Anastrozole & Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30642-2 Mayer et al. 2021 (PALLAS)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Palbociclib_99|Anastrozole & Palbociclib]]<br>2. [[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]<br>3. [[#Letrozole_.26_Palbociclib_99|Letrozole & Palbociclib]]<br>4. [[#Palbociclib_.26_Tamoxifen_99|Palbociclib & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for this arm of ATAC is based on the 2010 update for hormone-receptor positive patients.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''5-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 6-year course {{#subobject:ea2190|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30600-9 Tjan-Heijnen et al. 2017 (DATA)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Anastrozole_monotherapy_2|Anastrozole]] x 3 y
 
−
| style="background-color:#d9ef8b" |Might have superior DFS <br>(HR 0.79, 95% CI 0.62-1.02)
 
−
| style="background-color:#d73027" |More toxic
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3 y
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''6-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 7-year course {{#subobject:egja80|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2104162 Gnant et al. 2021 (SALSA)]
 
−
|2004-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_2|Anastrozole]] x 10 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|}
 
−
''Note: there does not appear to be a true comparator arm in this study design; this arm had a shorter duration and was less toxic.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''7-year course'''
 
−
</div></div>
 
−
===References===
 
−
# '''ATAC:''' Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002 Jun 22;359(9324):2131-9. Erratum in: Lancet 2002 Nov 9;360(9344):1520. [https://doi.org/10.1016/S0140-6736(02)09088-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12090977 PubMed] NCT00849030
 
−
## '''Update:''' Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [https://doi.org/10.1016/S0140-6736(04)17666-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15639680 PubMed]
 
−
## '''Update:''' Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M; Arimidex Tamoxifen Alone or in Combination (ATAC) Trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [https://doi.org/10.1016/S1470-2045%2807%2970385-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083636 PubMed]
 
−
## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. Epub 2010 Nov 17. [https://doi.org/10.1016/S1470-2045(10)70257-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21087898 PubMed]
 
−
# '''ABCSG-8:''' Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG; GABG. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://doi.org/10.1016/S0140-6736(05)67059-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16084253 PubMed] NCT00291759
 
−
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
−
## '''Update:''' Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [https://doi.org/10.1200/jco.2006.08.8054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17563395 PubMed]
 
−
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
## '''Update:''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.8993 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22271481 PubMed]
 
−
# '''ARNO 95:''' Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG; GABG. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://doi.org/10.1016/S0140-6736(05)67059-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16084253 PubMed]
 
−
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
−
## '''Update:''' Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [https://doi.org/10.1200/jco.2006.08.8054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17563395 PubMed]
 
−
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
## '''Update:''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.8993 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22271481 PubMed]
 
−
# '''ABCSG-6a:''' Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, Mlineritsch B, Tausch C, Stierer M, Hofbauer F, Renner K, Dadak C, Rücklinger E, Samonigg H; ABCSG. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007 Dec 19;99(24):1845-53. Epub 2007 Dec 11. Erratum in: J Natl Cancer Inst. 2008 Feb 6;100(3):226. [https://academic.oup.com/jnci/article/99/24/1845/2522241 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18073378 PubMed] NCT00300508
 
−
<!-- Presented at the 33rd Annual San Antonio Breast Cancer Symposium, December 8-12, 2010, San Antonio, TX. -->
 
−
# '''NCIC-CTG MA.27:''' Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC-CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. [https://doi.org/10.1200/jco.2012.44.7805 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23358971 PubMed] NCT00066573
 
−
# '''FACE:''' Smith I, Yardley D, Burris H, De Boer R, Amadori D, McIntyre K, Ejlertsen B, Gnant M, Jonat W, Pritchard KI, Dowsett M, Hart L, Poggio S, Comarella L, Salomon H, Wamil B, O'Shaughnessy J. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial. J Clin Oncol. 2017 Apr 1;35(10):1041-1048. Epub 2017 Jan 23. [https://doi.org/10.1200/JCO.2016.69.2871 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28113032 PubMed] NCT00248170
 
−
# '''DATA:''' Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, Swinkels ACP, Smorenburg CH, van der Sangen MJC, Kroep JR, De Graaf H, Honkoop AH, Erdkamp FLG, van den Berkmortel FWPJ, de Boer M, de Roos WK, Linn SC, Imholz ALT, Seynaeve CM; BOOG. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1502-1511. Epub 2017 Oct 12. Erratum in: Lancet Oncol. 2017 Nov;18(11):e642. [https://doi.org/10.1016/S1470-2045(17)30600-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29031778 PubMed] NCT00301457
 
−
# '''FATA-GIM3:''' De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. Epub 2018 Feb 23. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. [https://doi.org/10.1016/S1470-2045(18)30116-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29482983 PubMed] NCT00541086
 
−
# '''GEICAM/2006-10:''' Ruíz-Borrego M, Guerrero-Zotano A, Bermejo B, Ramos M, Cruz J, Baena-Cañada JM, Cirauqui B, Rodríguez-Lescure Á, Alba E, Martínez-Jáñez N, Muñoz M, Antolín S, Álvarez I, Del Barco S, Sevillano E, Chacón JI, Antón A, Escudero MJ, Ruiz V, Carrasco E, Martín M; GEICAM. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study. Breast Cancer Res Treat. 2019 Aug;177(1):115-125. Epub 2019 May 31. [https://doi.org/10.1007/s10549-019-05296-8 link to original article] '''contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/31152327 PubMed] NCT00543127
 
−
# '''PALLAS:''' Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. Epub 2021 Jan 15. [https://doi.org/10.1016/s1470-2045(20)30642-2 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33460574/ PubMed] NCT02513394
 
−
##'''Update:''' Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernández de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. Epub 2021 Dec 7. [https://doi.org/10.1200/jco.21.02554 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34874182/ PubMed]
 
−
# '''SALSA:''' Gnant M, Fitzal F, Rinnerthaler G, Steger GG, Greil-Ressler S, Balic M, Heck D, Jakesz R, Thaler J, Egle D, Manfreda D, Bjelic-Radisic V, Wieder U, Singer CF, Melbinger-Zeinitzer E, Haslbauer F, Sevelda P, Trapl H, Wette V, Wimmer K, Gampenrieder SP, Bartsch R, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Soelkner L, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group. Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer. N Engl J Med. 2021 Jul 29;385(5):395-405. [https://doi.org/10.1056/nejmoa2104162 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34320285/ PubMed] NCT00295620
 
−
# '''RxPONDER:''' NCT01272037
 
−
==Exemestane monotherapy {{#subobject:62ede3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2- to 3-year course {{#subobject:12d72f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa040331 Coombes et al. 2004 (IES)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#IES|See link]]
 
−
| style="background-color:#91cf60" |[[Complex_multipart_regimens#IES|See link]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62312-4 van de Velde et al. 2011 (TEAM)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#TEAM|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#TEAM|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The IES gave a range of 2 to 3 years of therapy. TEAM gave a range of 2 to 2.5 years of therapy.''
 
−
====Preceding treatment====
 
−
*[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3y
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''2 to 3 years, for a total of 5 years of hormonal therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 3-year course {{#subobject:4569f0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Preceding treatment====
 
−
*[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''3-year course, for a total of 5 years of hormonal therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 5-year course {{#subobject:31f118|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.14.0228 Mamounas et al. 2008 (NSABP B-33)]
 
−
|2001-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ Goss et al. 2013 (NCIC-CTG MA.27)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS60
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y, then AI x 3 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30642-2 Mayer et al. 2021 (PALLAS)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Palbociclib_99|Anastrozole & Palbociclib]]<br>2. [[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]<br>3. [[#Letrozole_.26_Palbociclib_99|Letrozole & Palbociclib]]<br>4. [[#Palbociclib_.26_Tamoxifen_99|Palbociclib & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*NSABP B-33: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''5-year course'''
 
−
</div></div>
 
−
===References===
 
−
# '''IES:''' Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [https://doi.org/10.1056/NEJMoa040331 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15014181 PubMed] NCT00038467
 
−
## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [https://doi.org/10.1016/S0140-6736(07)60200-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17307102 PubMed]
 
−
## '''Update:''' Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. [https://doi.org/10.1200/JCO.2010.33.7899 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22042946 PubMed]
 
−
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 
−
# '''NSABP B-33:''' Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.14.0228 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332472 PubMed] NCT00016432
 
−
# '''TEAM:''' van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [https://doi.org/10.1016/S0140-6736(10)62312-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21247627 PubMed] NCT00279448; NCT00032136; NCT00036270
 
−
## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [https://doi.org/10.1016/S1470-2045(17)30419-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28732650 PubMed]
 
−
<!-- Presented at the 33rd Annual San Antonio Breast Cancer Symposium, December 8-12, 2010, San Antonio, TX. -->
 
−
# '''NCIC-CTG MA.27:''' Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC-CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. [https://doi.org/10.1200/jco.2012.44.7805 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612593/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23358971 PubMed] NCT00066573
 
−
# '''FATA-GIM3:''' De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. Epub 2018 Feb 23. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. [https://doi.org/10.1016/S1470-2045(18)30116-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29482983 PubMed] NCT00541086
 
−
# '''PALLAS:''' Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. Epub 2021 Jan 15. [https://doi.org/10.1016/s1470-2045(20)30642-2 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33460574/ PubMed] NCT02513394
 
−
##'''Update:''' Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernández de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. Epub 2021 Dec 7. [https://doi.org/10.1200/jco.21.02554 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34874182/ PubMed]
 
−
==Letrozole monotherapy {{#subobject:55e6f9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2 years of therapy {{#subobject:3d1f97|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''2-year course'''
 
−
====Subsequent treatment====
 
−
*[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 3 y
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2 additional years of therapy {{#subobject:2c2390|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00352-1 Del Mastro et al. 2021 (GIM4)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 5 y
 
−
| style="background-color:#d73027" |Inferior iDFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. This is the lower bound of duration of therapy for GIM4.''
 
−
====Preceding treatment====
 
−
*GIM4: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3 y
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''2 additional years of endocrine therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 2.5 additional years of therapy {{#subobject:34f509|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/110/1/djx134/4093022/Optimal-Duration-of-Extended-Adjuvant-Endocrine Blok et al. 2017 (IDEAL)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 10 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. Continuation of treatment was started within 2 years of the completion of the first 5 years of treatment.''
 
−
====Preceding treatment====
 
−
*Any [[Regimen_classes#Endocrine_therapy|endocrine therapy]] for 5 years
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''2.5 additional years of endocrine therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 3 additional years of therapy {{#subobject:3c3390|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00352-1 Del Mastro et al. 2021 (GIM4)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 5 y
 
−
| style="background-color:#d73027" |Inferior iDFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. This is the upper bound of duration of therapy for GIM4.''
 
−
====Preceding treatment====
 
−
*BIG 1-98 & FATA-GIM3: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
*GIM4: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3 y
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''3 additional years of endocrine therapy'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 5 years of therapy {{#subobject:adcf9a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|rowspan=3|1998-2003
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|1. [[#Letrozole_monotherapy_2|Letrozole]], then [[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<sup>1</sup>
 
−
|
 
−
|-
 
−
|2. [[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup>
 
−
|
 
−
|-
 
−
|3. [[#Tamoxifen_monotherapy_2|Tamoxifen]], then [[#Letrozole_monotherapy_2|Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ Goss et al. 2016 (NCIC-CTG MA.17R)]
 
−
|NR-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 10 y
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|style="background-color:#eeee01"|No clinical difference in QoL
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.2871 Smith et al. 2017 (FACE)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Anastrozole_monotherapy_2|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y, then AI x 3 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.03639 Loibl et al. 2021 (PENELOPE-B)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Palbociclib_99|Anastrozole & Palbociclib]]<br>2. [[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]<br>3. [[#Letrozole_.26_Palbociclib_99|Letrozole & Palbociclib]]<br>4. [[#Palbociclib_.26_Tamoxifen_99|Palbociclib & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30642-2 Mayer et al. 2021 (PALLAS)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Palbociclib_99|Anastrozole & Palbociclib]]<br>2. [[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]<br>3. [[#Letrozole_.26_Palbociclib_99|Letrozole & Palbociclib]]<br>4. [[#Palbociclib_.26_Tamoxifen_99|Palbociclib & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for BIG 1-98 is based on the 2011 and 2018 updates.''<br>
 
−
''Note: PENELOPE-B did not specify the type of ET, leaving it to local discretion.''
 
−
====Preceding treatment====
 
−
*PENELOPE-B: Neoadjuvant [[Regimen_classes#Chemotherapy|chemotherapy]], then [[Surgery#Breast_cancer_surgery|surgery]], then [[Regimen_classes#Radiotherapy|RT]] per local guidelines
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''5-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 5 additional years of therapy {{#subobject:b467cc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa032312 Goss et al. 2003 (NCIC-CTG MA.17)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior DFS<br>DFS48: 93% vs 87%<br>(HR 0.57, 95% CI 0.43-0.75)
 
−
|style="background-color:#eeee01"|No clinical difference in QoL
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00352-1 Del Mastro et al. 2021 (GIM4)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 2-3 y
 
−
| style="background-color:#1a9850" |Superior iDFS<br>iDFS144: 67% vs 62%<br>(HR 0.78, 95% CI 0.65-0.93)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6691732/ Mamounas et al. 2018 (NSABP B-42)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<br>DFS84: 85% vs 81%<br>(HR 0.85, 95% CI 0.73-0.999)
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw055 Zdenkowski et al. 2016 (ANZ0501 LATER)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ Goss et al. 2016 (NCIC-CTG MA.17R)]
 
−
|NR-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 5 y
 
−
| style="background-color:#1a9850" |Superior DFS<br>DFS60: 95% vs 91%<br>(HR 0.66, 95% CI 0.48-0.91)
 
−
|style="background-color:#eeee01"|No clinical difference in QoL
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/110/1/djx134/4093022/Optimal-Duration-of-Extended-Adjuvant-Endocrine Blok et al. 2017 (IDEAL)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]] x 7.5 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30715-5 Colleoni et al. 2017 (SOLE)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_2|Letrozole]]; intermittent
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Continuation of treatment was started within 2 years of the completion of the first 5 years of treatment or immediately; see individual trials for details.''
 
−
====Preceding treatment====
 
−
*NCIC-CTG MA.17: Most patients received 5 years of [[#Tamoxifen_monotherapy_2|tamoxifen]] therapy prior to starting letrozole
 
−
*GIM4: [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3 y
 
−
*ANZ0501 LATER: At least 4 years of any [[Regimen_classes#Endocrine_therapy|endocrine therapy]]
 
−
*NCIC-CTG MA.17R: [[#Letrozole_monotherapy_2|Letrozole]] for 5 years
 
−
*IDEAL: Any [[Regimen_classes#Endocrine_therapy|endocrine therapy]] for 5 years
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''5 additional years of endocrine therapy'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCIC-CTG MA.17:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. [https://doi.org/10.1056/NEJMoa032312 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14551341 PubMed] NCT00003140
 
−
## '''Update:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC-CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. [http://jnci.oxfordjournals.org/content/97/17/1262.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16145047 PubMed]
 
−
## '''HRQoL analysis:''' Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12. [https://doi.org/10.1200/JCO.2005.11.181 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16157934 PubMed]
 
−
## '''Update:''' Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC-CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.12.6334 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332474 PubMed]
 
−
## '''Subgroup analysis:''' Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.11.6798 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332475 PubMed]
 
−
## '''Update:''' Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC-CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. [https://doi.org/10.1200/jco.2010.34.4010 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295549/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22042967 PubMed]
 
−
# '''BIG 1-98:''' Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A; BIG. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [https://doi.org/10.1056/NEJMoa052258 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16382061 PubMed] NCT00004205
 
−
## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [https://doi.org/10.1200/jco.2006.08.8617 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17200148 PubMed]
 
−
## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG; International Breast Cancer Study Group. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [https://doi.org/10.1016/S1470-2045%2807%2970386-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083065 PubMed]
 
−
## '''Subgroup analysis:''' Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.14.0459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332471 PubMed]
 
−
## '''Update:''' Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, Mauriac L, Forbes J, Price KN, Regan MM, Gelber RD, Coates AS; BIG. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009 Aug 20;361(8):766-76. [https://doi.org/10.1056/NEJMoa0810818 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921823/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19692688 PubMed]
 
−
## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG; International Breast Cancer Study Group. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [https://doi.org/10.1016/S1470-2045(11)70270-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22018631 PubMed]
 
−
## '''Update:''' Ruhstaller T, Giobbie-Hurder A, Colleoni M, Jensen MB, Ejlertsen B, de Azambuja E, Neven P, Láng I, Jakobsen EH, Gladieff L, Bonnefoi H, Harvey VJ, Spazzapan S, Tondini C, Del Mastro L, Veyret C, Simoncini E, Gianni L, Rochlitz C, Kralidis E, Zaman K, Jassem J, Piccart-Gebhart M, Di Leo A, Gelber RD, Coates AS, Goldhirsch A, Thürlimann B, Regan MM; BIG; International Breast Cancer Study Group. Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial. J Clin Oncol. 2019 Jan 10;37(2):105-114. Epub 2018 Nov 26. [https://doi.org/10.1200/JCO.18.00440 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325353/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30475668 PubMed]
 
−
# '''ANZ0501 LATER:''' Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. [https://doi.org/10.1093/annonc/mdw055 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26861603 PubMed] ACTRN12607000137493
 
−
# '''NCIC-CTG MA.17R:''' Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR. Extending aromatase-inhibitor adjuvant therapy to 10 Years. N Engl J Med. 2016 Jul 21;375(3):209-19. Epub 2016 Jun 5. [https://doi.org/10.1056/NEJMoa1604700 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024713/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27264120 PubMed] NCT00003140; NCT00754845
 
−
## '''HRQoL analysis:''' Lemieux J, Brundage MD, Parulekar WR, Goss PE, Ingle JN, Pritchard KI, Celano P, Muss H, Gralow J, Strasser-Weippl K, Whelan K, Tu D, Whelan TJ. Quality of life from Canadian Cancer Trials Group MA.17R: a randomized trial of extending adjuvant letrozole to 10 years. J Clin Oncol. 2018 Feb 20;36(6):563-571. Epub 2018 Jan 12. [https://doi.org/10.1200/JCO.2017.75.7500 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29328860 PubMed]
 
−
# '''FACE:''' Smith I, Yardley D, Burris H, De Boer R, Amadori D, McIntyre K, Ejlertsen B, Gnant M, Jonat W, Pritchard KI, Dowsett M, Hart L, Poggio S, Comarella L, Salomon H, Wamil B, O'Shaughnessy J. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial. J Clin Oncol. 2017 Apr 1;35(10):1041-1048. Epub 2017 Jan 23. [https://doi.org/10.1200/JCO.2016.69.2871 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28113032 PubMed] NCT00248170
 
−
# '''IDEAL:''' Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers GJ, Nortier JWR, Rutgers EJT, van de Velde CJH; IDEAL Study Group. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018 Jan 1;110(1). Epub 2017 Aug 23. [https://academic.oup.com/jnci/article-abstract/110/1/djx134/4093022/Optimal-Duration-of-Extended-Adjuvant-Endocrine link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28922787 PubMed] Eudra-CT 2006-003958-16
 
−
# '''SOLE:''' Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavilá J, Kuroi K, Marth C, Müller B, O'Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A; SOLE Investigators. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):127-138. Epub 2017 Nov 17. [https://doi.org/10.1016/S1470-2045(17)30715-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29158011 PubMed] NCT00553410
 
−
## '''HRQoL analysis:''' Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Biganzoli L, Müller B, Barbeaux A, Graas MP, Rabaglio M, Francis PA, Foukakis T, Pagani O, Graiff C, Vorobiof D, Maibach R, Di Leo A, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J; SOLE Investigators. Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial. Br J Cancer. 2019 May;120(10):959-967. Epub 2019 Apr 10. Erratum in: Br J Cancer. 2020 Jan 16 [https://www.nature.com/articles/s41416-019-0435-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6734915/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30967649 PubMed]
 
−
## '''Update:''' Jerusalem G, Farah S, Courtois A, Chirgwin J, Aebi S, Karlsson P, Neven P, Hitre E, Graas MP, Simoncini E, Abdi E, Kamby C, Thompson A, Loibl S, Gavilá J, Kuroi K, Marth C, Müller B, O'Reilly S, Gombos A, Ruhstaller T, Burstein HJ, Rabaglio M, Ruepp B, Ribi K, Viale G, Gelber RD, Coates AS, Loi S, Goldhirsch A, Regan MM, Colleoni M; SOLE Investigators. Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy. Ann Oncol. 2021 Oct;32(10):1256-1266. Epub 2021 Aug 10. [https://doi.org/10.1016/j.annonc.2021.07.017 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34384882/ PubMed]
 
−
# '''FATA-GIM3:''' De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. Epub 2018 Feb 23. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. [https://doi.org/10.1016/S1470-2045(18)30116-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29482983 PubMed] NCT00541086
 
−
# '''NSABP B-42:''' Mamounas EP, Bandos H, Lembersky BC, Jeong JH, Geyer CE Jr, Rastogi P, Fehrenbacher L, Graham ML, Chia SK, Brufsky AM, Walshe JM, Soori GS, Dakhil SR, Seay TE, Wade JL 3rd, McCarron EC, Paik S, Swain SM, Wickerham DL, Wolmark N. Use of letrozole after aromatase inhibitor-based therapy (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2019 Jan;20(1):88-99. Epub 2018 Nov 30. Erratum in: Lancet Oncol. 2019 Jan;20(1):e10. [https://doi.org/10.1016/S1470-2045(18)30621-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6691732/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30509771 PubMed] NCT00382070
 
−
# '''PALLAS:''' Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. Epub 2021 Jan 15. [https://doi.org/10.1016/s1470-2045(20)30642-2 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33460574/ PubMed] NCT02513394
 
−
##'''Update:''' Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernández de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. Epub 2021 Dec 7. [https://doi.org/10.1200/jco.21.02554 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34874182/ PubMed]
 
−
# '''PENELOPE-B:''' Loibl S, Marmé F, Martin M, Untch M, Bonnefoi H, Kim SB, Bear H, McCarthy N, Melé Olivé M, Gelmon K, García-Sáenz J, Kelly CM, Reimer T, Toi M, Rugo HS, Denkert C, Gnant M, Makris A, Koehler M, Huang-Bartelett C, Lechuga Frean MJ, Colleoni M, Werutsky G, Seiler S, Burchardi N, Nekljudova V, von Minckwitz G. Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial. J Clin Oncol. 2021 May 10;39(14):1518-1530. Epub 2021 Apr 1. [https://doi.org/10.1200/jco.20.03639 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/33793299/ PubMed] NCT01864746
 
−
# '''GIM4:''' Del Mastro L, Mansutti M, Bisagni G, Ponzone R, Durando A, Amaducci L, Campadelli E, Cognetti F, Frassoldati A, Michelotti A, Mura S, Urracci Y, Sanna G, Gori S, De Placido S, Garrone O, Fabi A, Barone C, Tamberi S, Bighin C, Puglisi F, Moretti G, Arpino G, Ballestrero A, Poggio F, Lambertini M, Montemurro F, Bruzzi P; Gruppo Italiano Mammella investigators. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1458-1467. Epub 2021 Sep 17. [https://doi.org/10.1016/s1470-2045(21)00352-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34543613/ PubMed] NCT01064635
 
−
==Tamoxifen monotherapy {{#subobject:2e0ab1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 year {{#subobject:97eecb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.3109/02841869209088914 Rydén et al. 1992 (SSBCG II:I)]
 
−
|NR
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Radiation_therapy_99|RT]]<br> 2. [[#Tamoxifen_.26_RT_99|Tamoxifen & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.14.3376 Knoop et al. 2001 (DBCG 77C)]
 
−
|1977-1982
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1994.12.10.2078 Rivkin et al. 1994 (SWOG S7827)]
 
−
|1979-1989
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer_-_historical#CMFVP|CMFVP]]<br> 2. [[#CMFVPT_99|CMFVPT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S0140-6736(98)09201-0 Overgaard et al. 1999 (DBCG 82C)]
 
−
|rowspan=2|1982-1990
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer#CMFT|CMFT]]
 
−
| style="background-color:#d73027" |Inferior DFS<sup>1</sup>
 
−
|-
 
−
|2. [[#Tamoxifen_.26_RT_88|Tamoxifen & RT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1080/02841860802014882 Andersen et al. 2008 (DBCG 89C)]
 
−
|1990-1994
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y<br> 2. [[#Tamoxifen.2FMegestrol_acetate_99|TAM/MA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for this arm of DBCG 82C versus CMFT is based on the 2013 update.''<br>
 
−
''Note: Knoop et al. 2001 is a retrospective biomarker analysis; we are not aware of another primary publication for DBCG 77C.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Mastectomy|Mastectomy]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
−
'''1-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2 years of 20 mg/day {{#subobject:bb9926|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(83)91683-5 Baum et al. 1983 (NATO)]
 
−
|1977-1981
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://annals.org/aim/fullarticle/699897 Cummings et al. 1985 (ECOG 1178)]
 
−
|1978-1982
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(88)90521-1 Bianco et al. 1988 (GUN)]
 
−
|1978-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/88/21/1543/922668 Rutqvist et al. 1996]
 
−
|1983-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/88/24/1834/890202 Baum & Odling-Smee 1996 (CRUK Over 50s)]
 
−
|NR-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.6.1701 Jakesz et al. 1999]
 
−
|1984-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#AV-CMF-T_99|AV-CMF-TAM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.06.116 Sacco et al. 2003 (SITAM 01)]
 
−
|1989-1996
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|[https://doi.org/10.1007/s10147-013-0657-z Shien et al. 2014 (JCOG9401)]
 
−
|1994-1999
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#ACT|ACT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ARNO 95)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#ARNO_95|See link]]
 
−
| style="background-color:#91cf60" |[[Complex_multipart_regimens#ARNO_95|See link]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ABCSG-8)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#ABCSG-8|See link]]
 
−
| style="background-color:#d9ef8b" |[[Complex_multipart_regimens#ABCSG-8|See link]]
 
−
|-
 
−
|[https://doi.org/10.1007/s12282-012-0394-6 Kimura et al. 2012]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Toremifene_monotherapy|Toremifene]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa040331 Coombes et al. 2004 (IES)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#IES|See link]]
 
−
| style="background-color:#91cf60" |[[Complex_multipart_regimens#IES|See link]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30116-5 De Placido et al. 2018 (FATA-GIM3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#FATA-GIM3|See link]]
 
−
|-
 
−
|}
 
−
''Note: IES gave a range of 2 to 3 years of therapy.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''2-year course'''
 
−
====Subsequent treatment====
 
−
*IES: [[#Exemestane_monotherapy_2|Exemestane]]
 
−
*BIG 1-98: [[#Letrozole_monotherapy_2|Letrozole]]
 
−
*ABCSG-8 & ARNO 95: [[#Anastrozole_monotherapy_2|Anastrozole]] x 3 y
 
−
*FATA-GIM3: [[#Anastrozole_monotherapy_2|Anastrozole]] versus [[#Exemestane_monotherapy_2|Exemestane]] versus [[#Letrozole_monotherapy_2|Letrozole]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 2 years of 30 mg/day {{#subobject:ff9926|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1080/0284186X.2017.1400179 Jensen et al. 2017 (CBC 02)]
 
−
|1975-1978
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.10.2731 Pritchard et al. 1996 (NCIC-CTG MA.4)]
 
−
|1984-1990
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
 
−
|[[Breast_cancer#CMFT|CMFT]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
−
**In CBC 02, the dose was 10 mg PO three times per day
 
−
'''2-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 2 years of 40 mg/d, then 3 years of 20 mg/day {{#subobject:7b8e78|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.01.138 Schmid et al. 2003 (ABCSG-6)]
 
−
|1990-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethemide_.26_Tamoxifen_99|Aminoglutethemide & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] as follows:
 
−
**Years 1 & 2: 40 mg PO once per day
 
−
**Years 3 to 5: 20 mg PO once per day
 
−
'''5-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 3 years of 20 mg/day {{#subobject:7a4c78|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(06)00908-7 Morales et al. 2006]
 
−
|1991-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#BIG_1-98|See link]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62312-4 van de Velde et al. 2011 (TEAM)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#TEAM|See link]]
 
−
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#TEAM|See link]]
 
−
|-
 
−
|}
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. TEAM gave a range of 2.5 to 3 years of therapy.''
 
−
====Preceding treatment====
 
−
*BIG 1-98: [[#Letrozole_monotherapy_2|Letrozole]] x 2y
 
−
*Morales et al. 2006: Adjuvant [[Regimen_classes#Chemotherapy|chemotherapy]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''3-year course'''
 
−
====Subsequent treatment====
 
−
*TEAM: [[#Exemestane_monotherapy_2|Exemestane]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 3 years of 30 mg/day {{#subobject:4f2c78|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdj022 Namer et al. 2006 (FASG 02)]
 
−
|1986-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-Tam_88|FEC50-Tam]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|[https://academic.oup.com/annonc/article/17/1/65/160873 Namer et al. 2006 (FASG 07)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FEC-Tam_88|FEC50-Tam]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.02.145 Fargeot et al. 2004 (FASG 08)]
 
−
|1991-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Tamoxifen_99|Epirubicin & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
−
'''3-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, 5 years {{#subobject:dc8bc3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(87)90762-8 Stewart et al. 1987 (Scottish Tamoxifen Trial)]
 
−
|1978-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198902233200802 Fisher et al. 1989 (NSABP B-14)]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>2</sup>
 
−
|
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/88/24/1828/890199 Tormey et al. 1996 (ECOG E4181/E5181)]
 
−
|1982-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]; indefinitely
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/88/21/1543/922668 Rutqvist et al. 1996]
 
−
|1983-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
 
−
|rowspan=2|1985-1988
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer_-_historical#ACT|ACT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#PFT|PFT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DDFS
 
−
|
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/7840523 Mustacchi et al. 1994 (GRETA)]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen alone (no surgery)]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/88/24/1834/890202 Baum & Odling-Smee 1996 (CRUK Over 50s)]
 
−
|NR-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
| style="background-color:#1a9850" |Superior EFS<sup>3</sup>
 
−
|
 
−
|-
 
−
|rowspan=2|[https://academic.oup.com/jnci/article/89/22/1673/2526493 Fisher et al. 1997 (NSABP B-20)]
 
−
|rowspan=2|1988-1993
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer#CMFT|CMFT]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>2</sup>
 
−
|
 
−
|-
 
−
|2. [[Stub#MFT|MFT]]
 
−
| style="background-color:#d3d3d3" |Not reported<sup>2</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.06.116 Sacco et al. 2003 (SITAM 01)]
 
−
|1989-1996
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2001.19.4.931 Fisher et al. 2001 (NSABP B-23)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S0140-6736(02)09088-8 Baum et al. 2002 (ATAC)]
 
−
| rowspan = "2"|1996-2000
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Tamoxifen_99|Anastrozole & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|2. [[#Anastrozole_monotherapy_2|Anastrozole]]
 
−
| style="background-color:#d73027" |Inferior DFS<sup>4</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.11396 Assikis et al. 2003]
 
−
|1986-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer_-_historical#FAC-MV|FAC-MV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.08.071 Hutchins et al. 2005 (INT-0102)]
 
−
|1989-1993
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ Albain et al. 2009 (SWOG-8814)]
 
−
|1989-1995
 
−
| style="background-color:#1a9851" |Phase 3
 
−
|[[Complex_multipart_regimens#SWOG-8814|See link]]
 
−
|[[Complex_multipart_regimens#SWOG-8814|See link]]
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.11.101 Fisher et al. 2002 (NSABP B-21)]
 
−
|1989-1998
 
−
|style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Radiation_therapy_88|RT]]<br> 2. [[#Tamoxifen_.26_RT_88|Tamoxifen & RT]]
 
−
| style="background-color:#d73027" |Inferior DFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa040595 Fyles et al. 2004]
 
−
|1992-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa040587 Hughes et al. 2004 (CALGB 9343)]
 
−
|1994-1999
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947231/ Rao et al. 2010 (ECOG EB193)]
 
−
|1995-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fenretinide_.26_Tamoxifen_77|Fenretinide & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.33.7006 Pritchard et al. 2011 (NCIC-CTG MA.14)]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_Octreotide_LAR_99|Tamoxifen & Octreotide LAR]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ARNO 95)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2y, then [[#Anastrozole_monotherapy_2|Anastrozole]] x 3y
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67059-6 Jakesz et al. 2005 (ABCSG-8)]
 
−
|1996-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2y, then [[#Anastrozole_monotherapy_2|Anastrozole]] x 3y
 
−
| style="background-color:#fee08b" |Might have inferior RFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)61963-1 Davies et al. 2013 (ATLAS)]
 
−
|1996-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 10y
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa040331 Coombes et al. 2004 (IES)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2-3y, then [[#Exemestane_monotherapy_2|Exemestane]] x 2-3y
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>5</sup>
 
−
|
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1056/NEJMoa052258 Thürlimann et al. 2005 (BIG 1-98)]
 
−
|rowspan=3|1998-2003
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Letrozole_monotherapy_2|Letrozole]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>6</sup>
 
−
|
 
−
|-
 
−
|2. [[#Letrozole_monotherapy_2|Letrozole]] x 2y, then [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 3y
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|
 
−
|-
 
−
|3. [[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2y, then [[#Letrozole_monotherapy_2|Letrozole]] x 3y
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.14.0228 Mamounas et al. 2008 (NSABP B-33)]
 
−
|2001-2003
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62312-4 van de Velde et al. 2011 (TEAM)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 2.5-3y, then [[#Exemestane_monotherapy_2|Exemestane]] x 2-2.5y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS60
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-010-0888-x Aihara et al. 2010 (N-SAS BC03)]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 1-4y, then [[#Anastrozole_monotherapy_2|Anastrozole]] x 1-4y (5y total)
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
| style="background-color:#ffffbf" |Similar toxicity
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172658/ Sparano et al. 2018 (TAILORx)]
 
−
|2006-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2108873 Kalinsky et al. 2021 (RxPONDER)]
 
−
|2011-2017
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30642-2 Mayer et al. 2021 (PALLAS)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Palbociclib_99|Anastrozole & Palbociclib]]<br>2. [[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]<br>3. [[#Letrozole_.26_Palbociclib_99|Letrozole & Palbociclib]]<br>4. [[#Palbociclib_.26_Tamoxifen_99|Palbociclib & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for the Scottish Tamoxifen Trial is based on the 2001 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for NSABP B-14 & NSABP B-20 is based on the 2004 update.''<br>
 
−
''<sup>3</sup>Reported efficacy for CRUK Over 50s is based on the 2011 update.''<br>
 
−
''<sup>4</sup>Reported efficacy for this arm of ATAC is based on the 2010 update for hormone-receptor positive patients.''<br>
 
−
''<sup>5</sup>Reported efficacy for IES is based on the 2011 update.''<br>
 
−
''<sup>6</sup>Reported efficacy for BIG 1-98 is based on the 2011 & 2018 updates.''<br>
 
−
''Note: in Fyles et al. 2004 and CALGB 9343, the randomization was to radiation therapy or no radiation therapy; all patients received 5 years of tamoxifen.''
 
−
====Preceding treatment====
 
−
*NSABP B-23: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#CMF|CMF]] x 6 versus [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4
 
−
*INT-0102: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC|CAF]] x 6 versus [[Breast_cancer#CMF|CMF]] x 6
 
−
*SWOG-8814: [[Surgery#Breast_cancer_surgery|Surgery]] versus [[Surgery#Breast_cancer_surgery|surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6
 
−
*TAILORx: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4 or [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|q3wk T]] x 4 or [[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4, then [[Breast_cancer#Paclitaxel_monotherapy.2C_dose-dense_.28q2wk.29_2|ddT]] x 4 or [[Breast_cancer#CMF|CMF]] x 6 to 8 or [[Breast_cancer#FEC_2|FEC]] x 6 or [[Breast_cancer#TAC_.28Docetaxel.29_2|TAC]] x 4 to 6 or [[Breast_cancer#DC|TC]] x 4 versus [[Breast_cancer_-_null_regimens#Observation|no chemotherapy]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
**Some older trials report using 10 mg PO twice per day
 
−
'''5-year course'''
 
−
====Subsequent treatment====
 
−
*NSABP B-33: [[#Exemestane_monotherapy_2|Exemestane]] versus [[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
*TAILORx, post-menopausal at year 6: [[:Category:Aromatase_inhibitors|AI]] x 5 years
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, 10 years {{#subobject:43a51a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)61963-1 Davies et al. 2013 (ATLAS)]
 
−
|1996-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]] x 5 years
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''10-year course'''
 
−
</div></div>
 
−
===References===
 
−
# '''NATO:''' Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Lea JC, Richards D, Ellis SH. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer: interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet. 1983 Feb 5;1(8319):257-61. [https://doi.org/10.1016/S0140-6736(83)91683-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6130291 PubMed]
 
−
## '''Update:''' Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Richards D, Ellis SH. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer: analysis at six years by Nolvadex Adjuvant Trial Organisation. Lancet. 1985 Apr 13;1(8433):836-40. [https://doi.org/10.1016/S0140-6736(85)92206-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2858709 PubMed]
 
−
# '''ECOG 1178:''' Cummings FJ, Gray R, Davis TE, Tormey DC, Harris JE, Falkson G, Arseneau J. Adjuvant tamoxifen treatment of elderly women with stage II breast cancer: a double-blind comparison with placebo. Ann Intern Med. 1985 Sep;103(3):324-9. [https://annals.org/aim/fullarticle/699897 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3896085 PubMed]
 
−
# '''Scottish Tamoxifen Trial:''' Stewart HJ, Taylor W, Forrest P. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial: report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. Lancet. 1987 Jul 25;2(8552):171-5. [https://doi.org/10.1016/S0140-6736(87)90762-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2885637 PubMed]
 
−
## '''Update:''' Stewart HJ, Forrest AP, Everington D, McDonald CC, Dewar JA, Hawkins RA, Prescott RJ, George WD; Scottish Cancer Trials Breast Group. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. Br J Cancer. 1996 Jul;74(2):297-9. [https://www.nature.com/articles/bjc1996356 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074573/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/8688340 PubMed]
 
−
## '''Update:''' Stewart HJ, Prescott RJ, Forrest AP. Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst. 2001 Mar 21;93(6):456-62. [https://academic.oup.com/jnci/article/93/6/456/2906503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11259471 PubMed]
 
−
# '''GUN:''' Bianco AR, De Placido S, Gallo C, Pagliarulo C, Marinelli A, Petrella G, D'Istria M, Delrio G. Adjuvant therapy with tamoxifen in operable breast cancer: 10 year results of the Naples (GUN) study. Lancet. 1988 Nov 12;2(8620):1095-9. [https://doi.org/10.1016/S0140-6736(88)90521-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2903322 PubMed]
 
−
# '''NSABP B-14:''' Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, Dimitrov NV, Wolmark N, Wickerham DL, Fisher ER, Margolese R, Robidoux A, Shibata H, Terz J, Peterson AHG, Feldman MI, Farrar W, Evans J, Lickley HL, Ketner M. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989 Feb 23;320(8):479-84. [https://doi.org/10.1056/NEJM198902233200802 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2644532 PubMed]
 
−
## '''Update:''' Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschênes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AH, Feldman MI, Farrar W, Evans J, Lickley HL. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996 Nov 6;88(21):1529-42. [https://academic.oup.com/jnci/article/88/21/1529/922662 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8901851 PubMed]
 
−
## '''Update:''' Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001 May 2;93(9):684-90. [https://academic.oup.com/jnci/article/93/9/684/2906559 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11333290 PubMed]
 
−
## '''Pooled update:''' Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N; National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004 Sep 4-10;364(9437):858-68. [https://doi.org/10.1016/S0140-6736(04)16981-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/15351193 PubMed]
 
−
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://doi.org/10.1200/JCO.1990.8.6.1005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2189950 PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
# '''SSBCG II:I:''' Rydén S, Fernö M, Möller T, Aspegren K, Bergljung L, Killander D, Landberg T. Long-term effects of adjuvant tamoxifen and/or radiotherapy: the South Sweden Breast Cancer Trial. Acta Oncol. 1992;31(2):271-4. [https://doi.org/10.3109/02841869209088914 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1622645 PubMed]
 
−
## '''Update:''' Killander F, Anderson H, Rydén S, Möller T, Aspegren K, Ceberg J, Danewid C, Malmström P. Radiotherapy and tamoxifen after mastectomy in postmenopausal women -- 20 year follow-up of the South Sweden Breast Cancer Group randomised trial SSBCG II:I. Eur J Cancer. 2007 Sep;43(14):2100-8. Epub 2007 Jul 17. [https://www.ejcancer.com/article/S0959-8049(07)00439-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/17644330 PubMed]
 
−
# '''GRETA:''' Mustacchi G, Milani S, Pluchinotta A, De Matteis A, Rubagotti A, Perrota A; Group for Research on Endocrine Therapy in the Elderly. Tamoxifen or surgery plus tamoxifen as primary treatment for elderly patients with operable breast cancer: the GRETA trial. Anticancer Res. 1994 Sep-Oct;14(5B):2197-200. [https://pubmed.ncbi.nlm.nih.gov/7840523 PubMed]
 
−
## '''Update:''' Mustacchi G, Ceccherini R, Milani S, Pluchinotta A, De Matteis A, Maiorino L, Farris A, Scanni A, Sasso F; Italian Cooperative Group GRETA. Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial. Ann Oncol. 2003 Mar;14(3):414-20. [https://doi.org/10.1093/annonc/mdg117 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12598347 PubMed]
 
−
## '''Update:''' Mustacchi G, Scanni A, Capasso I, Farris A, Pluchinotta A, Isola G. Update of the phase III trial 'GRETA' of surgery and tamoxifen versus tamoxifen alone for early breast cancer in elderly women. Future Oncol. 2015;11(6):933-41. Epub 2014 Nov 10. [https://www.futuremedicine.com/doi/abs/10.2217/fon.14.266 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25383659 PubMed]
 
−
# '''SWOG S7827:''' Rivkin SE, Green S, Metch B, Cruz AB, Abeloff MD, Jewell WR, Costanzi JJ, Farrar WB, Minton JP, Osborne CK. Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study. J Clin Oncol. 1994 Oct;12(10):2078-85. [https://doi.org/10.1200/JCO.1994.12.10.2078 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7931477 PubMed]
 
−
# '''NCIC-CTG MA.4:''' Pritchard KI, Paterson AH, Paul NA, Zee B, Fine S, Pater J; National Cancer Institute of Canada Clinical Trials Group. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. J Clin Oncol. 1996 Oct;14(10):2731-7. [https://doi.org/10.1200/JCO.1996.14.10.2731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8874334 PubMed]
 
−
## '''Update:''' Pritchard KI, Paterson AH, Fine S, Paul NA, Zee B, Shepherd LE, Abu-Zahra H, Ragaz J, Knowling M, Levine MN, Verma S, Perrault D, Walde PL, Bramwell VH, Poljicak M, Boyd N, Warr D, Norris BD, Bowman D, Armitage GR, Weizel H, Buckman RA; NCIC-CTG. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1997 Jun;15(6):2302-11. [https://doi.org/10.1200/JCO.1997.15.6.2302 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9196144 PubMed]
 
−
# Rutqvist LE, Hatschek T, Rydén S, Bergh J, Bengtsson NO, Carstenssen J, Nordenskjöld B, Wallgren A; Swedish Breast Cancer Cooperative Group. Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. J Natl Cancer Inst. 1996 Nov 6;88(21):1543-9. [https://academic.oup.com/jnci/article/88/21/1543/922668 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8901852 PubMed]
 
−
# '''ECOG E4181/E5181:''' Tormey DC, Gray R, Falkson HC; [[Study_Groups#ECOG|ECOG]]. Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. J Natl Cancer Inst. 1996 Dec 18;88(24):1828-33. [https://academic.oup.com/jnci/article/88/24/1828/890199 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8961972 PubMed]
 
−
# '''CRUK Over 50s:''' Baum M, Odling-Smee W; Current Trials working Party of the Cancer Research Campaign Breast Cancer Trials Group. Preliminary results from the cancer research campaign trial evaluating tamoxifen duration in women aged fifty years or older with breast cancer. J Natl Cancer Inst. 1996 Dec 18;88(24):1834-9. Erratum in: J Natl Cancer Inst 1997 Apr 16;89(8):590. [https://academic.oup.com/jnci/article/88/24/1834/890202 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8961973 PubMed]
 
−
## '''Update:''' Hackshaw A, Roughton M, Forsyth S, Monson K, Reczko K, Sainsbury R, Baum M. Long-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol. 2011 May 1;29(13):1657-63. Epub 2011 Mar 21. [https://doi.org/10.1200/JCO.2010.32.2933 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21422412 PubMed]
 
−
# '''NSABP B-20:''' Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL, Bryant J, Dimitrov NV, Abramson N, Atkins JN, Shibata H, Deschenes L, Margolese RG. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997 Nov 19;89(22):1673-82. [https://academic.oup.com/jnci/article/89/22/1673/2526493 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9390536 PubMed]
 
−
## '''Pooled update:''' Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N; National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004 Sep 4-10;364(9437):858-68. [https://doi.org/10.1016/S0140-6736(04)16981-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/15351193 PubMed]
 
−
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
# '''DBCG 82C:''' Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999 May 15;353(9165):1641-8. [https://doi.org/10.1016/S0140-6736(98)09201-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10335782 PubMed]
 
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## '''Update:''' Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. [https://www.ejcancer.com/article/S0959-8049(13)00383-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23756360 PubMed]
 
−
# Jakesz R, Hausmaninger H, Haider K, Kubista E, Samonigg H, Gnant M, Manfreda D, Tschurtschenthaler G, Kolb R, Stierer M, Fridrik M, Mlineritsch B, Steindorfer P, Mittlböck M, Steger G; ABCSG. Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer. J Clin Oncol. 1999 Jun;17(6):1701-9. [https://doi.org/10.1200/JCO.1999.17.6.1701 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10561206 PubMed]
 
−
# '''NSABP B-23:''' Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [https://doi.org/10.1200/jco.2001.19.4.931 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181655 PubMed]
 
−
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
# '''DBCG 77C:''' Knoop AS, Bentzen SM, Nielsen MM, Rasmussen BB, Rose C. Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. J Clin Oncol. 2001 Jul 15;19(14):3376-84. [https://doi.org/10.1200/JCO.2001.19.14.3376 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11454885 PubMed]
 
−
# '''ATAC:''' Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002 Jun 22;359(9324):2131-9. Erratum in: Lancet 2002 Nov 9;360(9344):1520. [https://doi.org/10.1016/S0140-6736(02)09088-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12090977 PubMed] NCT00849030
 
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## '''Update:''' Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [https://doi.org/10.1016/S0140-6736(04)17666-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15639680 PubMed]
 
−
## '''Update:''' Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M; Arimidex Tamoxifen Alone or in Combination (ATAC) Trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [https://doi.org/10.1016/S1470-2045%2807%2970385-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083636 PubMed]
 
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## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. Epub 2010 Nov 17. [https://doi.org/10.1016/S1470-2045(10)70257-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21087898 PubMed]
 
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# '''NSABP B-21:''' Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Nesbitt L, Paik S, Pisansky TM, Wolmark N; National Surgical Adjuvant Breast and Bowel Project. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002 Oct 15;20(20):4141-9. [https://doi.org/10.1200/JCO.2002.11.101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12377957 PubMed]
 
−
# '''ABCSG-6:''' Schmid M, Jakesz R, Samonigg H, Kubista E, Gnant M, Menzel C, Seifert M, Haider K, Taucher S, Mlineritsch B, Steindorfer P, Kwasny W, Stierer M, Tausch C, Fridrik M, Wette V, Steger G, Hausmaninger H; ABCSG. Randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide as adjuvant treatment in postmenopausal breast cancer patients with hormone receptor-positive disease: Austrian breast and colorectal cancer study group trial 6. J Clin Oncol. 2003 Mar 15;21(6):984-90. [https://doi.org/10.1200/jco.2003.01.138 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12637461 PubMed] NCT00309491
 
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# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [https://doi.org/10.1002/cncr.11396 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12767083 PubMed]
 
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# '''SITAM 01:''' Sacco M, Valentini M, Belfiglio M, Pellegrini F, De Berardis G, Franciosi M, Nicolucci A; Italian Interdisciplinary Group for Cancer Care Evaluation. Randomized trial of 2 versus 5 years of adjuvant tamoxifen for women aged 50 years or older with early breast cancer: Italian Interdisciplinary Group Cancer Evaluation Study of Adjuvant Treatment in Breast Cancer 01. J Clin Oncol. 2003 Jun 15;21(12):2276-81. [https://doi.org/10.1200/jco.2003.06.116 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12805326/ PubMed]
 
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##'''Update:''' Belfiglio M, Valentini M, Pellegrini F, De Berardis G, Franciosi M, Rossi MC, Sacco M, Nicolucci A; Interdisciplinary Group for Cancer Care Evaluated (GIVIO) Group. Twelve-year mortality results of a randomized trial of 2 versus 5 years of adjuvant tamoxifen for postmenopausal early-stage breast carcinoma patients (SITAM 01). Cancer. 2005 Dec 1;104(11):2334-9. [https://doi.org/10.1002/cncr.21474 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16245354/ PubMed]
 
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# '''IES:''' Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [https://doi.org/10.1056/NEJMoa040331 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15014181 PubMed] NCT00038467
 
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## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [https://doi.org/10.1016/S0140-6736(07)60200-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17307102 PubMed]
 
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## '''Update:''' Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. [https://doi.org/10.1200/JCO.2010.33.7899 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22042946 PubMed]
 
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# Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):963-70. [https://doi.org/10.1056/NEJMoa040595 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15342804 PubMed]
 
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# '''CALGB 9343:''' Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; [[Study_Groups#CALGB|CALGB]]; Radiation Therapy Oncology Group; [[Study_Groups#ECOG|ECOG]]. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. [https://doi.org/10.1056/NEJMoa040587 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15342805 PubMed]
 
−
## '''Update:''' Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013 Jul 1;31(19):2382-7. Epub 2013 May 20. [https://doi.org/10.1200/jco.2012.45.2615 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691356/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23690420 PubMed]
 
−
# '''IBCSG 12-93/IBCSG 14-93:''' Pagani O, Gelber S, Price K, Zahrieh D, Gelber R, Simoncini E, Castiglione-Gertsch M, Coates AS, Goldhirsch A; International Breast Cancer Study Group. Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol. 2004 Dec;15(12):1749-59. [https://doi.org/10.1093/annonc/mdh463 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15550579/ PubMed] NCT00002529
 
−
# '''FASG 08:''' Fargeot P, Bonneterre J, Roché H, Lortholary A, Campone M, Van Praagh I, Monnier A, Namer M, Schraub S, Barats JC, Guastalla JP, Goudier MJ, Chapelle-Marcillac I. Disease-free survival advantage of weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast cancer patients: 6-year follow-up results of the French Adjuvant Study Group 08 trial. J Clin Oncol. 2004 Dec 1;22(23):4622-30. Epub 2004 Oct 25. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. [https://doi.org/10.1200/JCO.2004.02.145 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15505276 PubMed]
 
−
# '''Review:''' Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. [https://doi.org/10.1016/S0140-6736(05)66544-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15894097 PubMed]
 
−
# '''ABCSG-8:''' Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG; GABG. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://doi.org/10.1016/S0140-6736(05)67059-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16084253 PubMed] NCT00291759
 
−
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
−
## '''Update:''' Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [https://doi.org/10.1200/jco.2006.08.8054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17563395 PubMed]
 
−
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
## '''Update:''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.8993 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22271481 PubMed]
 
−
# '''ARNO 95:''' Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J; ABCSG; GABG. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005 Aug 6-12;366(9484):455-62. [https://doi.org/10.1016/S0140-6736(05)67059-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16084253 PubMed]
 
−
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. -->
 
−
## '''Update:''' Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [https://doi.org/10.1200/jco.2006.08.8054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17563395 PubMed]
 
−
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. -->
 
−
## '''Update:''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.8993 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22271481 PubMed]
 
−
# '''INT-0102:''' Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [https://doi.org/10.1200/jco.2005.08.071 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293862 PubMed]
 
−
# '''BIG 1-98:''' Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A; BIG. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [https://doi.org/10.1056/NEJMoa052258 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16382061 PubMed] NCT00004205
 
−
## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [https://doi.org/10.1200/jco.2006.08.8617 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17200148 PubMed]
 
−
## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG' International Breast Cancer Study Group. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [https://doi.org/10.1016/S1470-2045%2807%2970386-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083065 PubMed]
 
−
## '''Subgroup analysis:''' Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.14.0459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332471 PubMed]
 
−
## '''Update:''' Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, Mauriac L, Forbes J, Price KN, Regan MM, Gelber RD, Coates AS; BIG. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009 Aug 20;361(8):766-76. [https://doi.org/10.1056/NEJMoa0810818 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921823/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19692688 PubMed]
 
−
## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG; International Breast Cancer Study Group. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [https://doi.org/10.1016/S1470-2045(11)70270-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22018631 PubMed]
 
−
## '''Update:''' Ruhstaller T, Giobbie-Hurder A, Colleoni M, Jensen MB, Ejlertsen B, de Azambuja E, Neven P, Láng I, Jakobsen EH, Gladieff L, Bonnefoi H, Harvey VJ, Spazzapan S, Tondini C, Del Mastro L, Veyret C, Simoncini E, Gianni L, Rochlitz C, Kralidis E, Zaman K, Jassem J, Piccart-Gebhart M, Di Leo A, Gelber RD, Coates AS, Goldhirsch A, Thürlimann B, Regan MM; BIG; International Breast Cancer Study Group. Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial. J Clin Oncol. 2019 Jan 10;37(2):105-114. Epub 2018 Nov 26. [https://doi.org/10.1200/JCO.18.00440 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325353/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30475668 PubMed]
 
−
# '''FASG 02; FASG 07:''' Namer M, Fargeot P, Roché H, Campone M, Kerbrat P, Romestaing P, Monnier A, Luporsi E, Montcuquet P, Bonneterre J; French Adjuvant Study Group. Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials. Ann Oncol. 2006 Jan;17(1):65-73. [https://doi.org/10.1093/annonc/mdj022 link to original article] '''contains article''' [https://pubmed.ncbi.nlm.nih.gov/16361531 PubMed]
 
−
# Morales L, Canney P, Dyczka J, Rutgers E, Coleman R, Cufer T, Welnicka-Jaskiewicz M, Nortier J, Bogaerts J, Therasse P, Paridaens R; [[Study_Groups#EORTC|EORTC]] Breast Group; Scottish Breast Cancer Trials Group. Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group. Eur J Cancer. 2007 Jan;43(2):331-40. Epub 2006 Nov 28. [https://www.ejcancer.com/article/S0959-8049(06)00908-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17134892 PubMed]
 
−
# '''DBCG 89C:''' Andersen J, Kamby C, Ejlertsen B, Cold S, Ewertz M, Jacobsen EH, Philip P, Møller KA, Jensen D, Møller S. Tamoxifen for one year versus two years versus 6 months of Tamoxifen and 6 months of megestrol acetate: a randomized comparison in postmenopausal patients with high-risk breast cancer (DBCG 89C). Acta Oncol. 2008;47(4):718-24. [https://doi.org/10.1080/02841860802014882 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18465340 PubMed]
 
−
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 
−
# '''NSABP B-33:''' Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [https://doi.org/10.1200/jco.2007.14.0228 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18332472 PubMed] NCT00016432
 
−
# '''SWOG-8814:''' Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. [https://doi.org/10.1016/S0140-6736(09)61523-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20004966 PubMed] NCT00929591
 
−
# '''N-SAS BC03:''' Aihara T, Takatsuka Y, Ohsumi S, Aogi K, Hozumi Y, Imoto S, Mukai H, Iwata H, Watanabe T, Shimizu C, Nakagami K, Tamura M, Ito T, Masuda N, Ogino N, Hisamatsu K, Mitsuyama S, Abe H, Tanaka S, Yamaguchi T, Ohashi Y. Phase III randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in Japanese postmenopausal women with hormone-responsive breast cancer: N-SAS BC03 study. Breast Cancer Res Treat. 2010 Jun;121(2):379-87. [https://doi.org/10.1007/s10549-010-0888-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20390343 PubMed] UMIN C000000056
 
−
# '''ECOG EB193:''' Rao RD, Cobleigh MA, Gray R, Graham ML 2nd, Norton L, Martino S, Budd GT, Ingle JN, Wood WC. Phase III double-blind, placebo-controlled, prospective randomized trial of adjuvant tamoxifen vs tamoxifen and fenretinide in postmenopausal women with positive receptors (EB193): an intergroup trial coordinated by the Eastern Cooperative Oncology Group. Med Oncol. 2011 Dec;28 Suppl 1:S39-47. Epub 2010 Sep 28. [https://doi.org/10.1007/s12032-010-9682-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947231/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20878269 PubMed] NCT00002646
 
−
# '''TEAM:''' van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [https://doi.org/10.1016/S0140-6736(10)62312-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21247627 PubMed] NCT00279448; NCT00032136; NCT00036270
 
−
## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [https://doi.org/10.1016/S1470-2045(17)30419-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28732650 PubMed]
 
−
# '''NCIC-CTG MA.14:''' Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O'Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN. Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC-CTG MA.14. J Clin Oncol. 2011 Oct 10;29(29):3869-76. Epub 2011 Sep 12. [https://doi.org/10.1200/JCO.2010.33.7006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21911723 PubMed] NCT00002864
 
−
## '''Update:''' Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC-CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. Epub 2015 Aug 15. [http://link.springer.com/article/10.1007/s10549-015-3547-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681581/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26276354 PubMed]
 
−
# Kimura M, Tominaga T, Kimijima I, Takatsuka Y, Takashima S, Nomura Y, Kasumi F, Yamaguchi A, Masuda N, Noguchi S, Eshima N. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer. Breast Cancer. 2014 May;21(3):275-83. Epub 2012 Sep 12. [https://doi.org/10.1007/s12282-012-0394-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22968626 PubMed]
 
−
# '''ATLAS:''' Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Erratum in: Lancet. 2013 Mar 9;381(9869):804. [https://doi.org/10.1016/S0140-6736(12)61963-1 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596060/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23219286 PubMed] NCT00003016
 
−
# '''JCOG9401:''' Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. [https://doi.org/10.1007/s10147-013-0657-z link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24395447 PubMed]
 
−
# '''CBC 02:''' Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen Breast Cancer Trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. [https://doi.org/10.1080/0284186X.2017.1400179 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29165021 PubMed]
 
−
# '''FATA-GIM3:''' De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, Riccardi F, Russo A, Del Mastro L, Cogoni AA, Cognetti F, Gori S, Foglietta J, Frassoldati A, Amoroso D, Laudadio L, Moscetti L, Montemurro F, Verusio C, Bernardo A, Lorusso V, Gravina A, Moretti G, Lauria R, Lai A, Mocerino C, Rizzo S, Nuzzo F, Carlini P, Perrone F; GIM Investigators. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):474-485. Epub 2018 Feb 23. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. [https://doi.org/10.1016/S1470-2045(18)30116-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29482983 PubMed] NCT00541086
 
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# '''TAILORx:''' Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018 Jul 12;379(2):111-121. Epub 2018 Jun 3. [https://doi.org/10.1056/NEJMoa1804710 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172658/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/29860917 PubMed] NCT00310180
 
−
# '''PALLAS:''' Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. Epub 2021 Jan 15. [https://doi.org/10.1016/s1470-2045(20)30642-2 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33460574/ PubMed] NCT02513394
 
−
##'''Update:''' Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernández de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. Epub 2021 Dec 7. [https://doi.org/10.1200/jco.21.02554 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34874182/ PubMed]
 
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# '''RxPONDER:''' Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, Lin NU, Perez EA, Goldstein LJ, Chia SKL, Dhesy-Thind S, Rastogi P, Alba E, Delaloge S, Martin M, Kelly CM, Ruiz-Borrego M, Gil-Gil M, Arce-Salinas CH, Brain EGC, Lee ES, Pierga JY, Bermejo B, Ramos-Vazquez M, Jung KH, Ferrero JM, Schott AF, Shak S, Sharma P, Lew DL, Miao J, Tripathy D, Pusztai L, Hortobagyi GN. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021 Dec 16;385(25):2336-2347. Epub 2021 Dec 1. [https://doi.org/10.1056/nejmoa2108873 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34914339/ PubMed] NCT01272037
 
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# '''SWOG S1207:''' NCT01674140
 
−
==Toremifene monotherapy {{#subobject:4feb63|Regimen=1}}==
 
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<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 40 mg/day x 2y {{#subobject:b872bf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s12282-012-0394-6 Kimura et al. 2012]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Toremifene (Fareston)]] 40 mg PO once per day
 
−
'''2-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 40 mg/day x 5y {{#subobject:b8iyaf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30534-9 Toi et al. 2021]
 
−
|2012-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_.26_Toremifene_88|S-1 & Toremifene]]
 
−
| style="background-color:#d73027" |Inferior IDFS
 
−
|-
 
−
|}
 
−
''Note: this is the lower bound of a range specified by Toi et al. 2021.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Toremifene (Fareston)]] 40 mg PO once per day
 
−
'''5-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 60 mg/day x 5y {{#subobject:bjbuzf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh463 Pagani et al. 2004 (IBCSG 12-93/IBCSG 14-93)]
 
−
|1993-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#eeee01" |Non-inferior DFS<sup>1</sup><br>DFS60: 72% vs 69%<br>(RR 0.95, 95% CI 0.76-1.18)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>It is not clear from the manuscript whether these trials had a non-inferiority design, but it appears to be the case.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Toremifene (Fareston)]] 40 mg PO once per day
 
−
'''5-year course'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 120 mg/day x 5y {{#subobject:b8i9wa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30534-9 Toi et al. 2021]
 
−
|2012-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_.26_Toremifene_88|S-1 & Toremifene]]
 
−
| style="background-color:#d73027" |Inferior IDFS
 
−
|-
 
−
|}
 
−
''Note: this is the upper bound of a range specified by Toi et al. 2021.''
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
====Endocrine therapy====
 
−
*[[Toremifene (Fareston)]] 120 mg PO once per day
 
−
'''5-year course'''
 
−
</div></div>
 
−
===References===
 
−
# '''IBCSG 12-93/IBCSG 14-93:''' Pagani O, Gelber S, Price K, Zahrieh D, Gelber R, Simoncini E, Castiglione-Gertsch M, Coates AS, Goldhirsch A; International Breast Cancer Study Group. Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol. 2004 Dec;15(12):1749-59. [https://doi.org/10.1093/annonc/mdh463 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15550579/ PubMed] NCT00002529
 
−
# Kimura M, Tominaga T, Kimijima I, Takatsuka Y, Takashima S, Nomura Y, Kasumi F, Yamaguchi A, Masuda N, Noguchi S, Eshima N. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer. Breast Cancer. 2014 May;21(3):275-83. Epub 2012 Sep 12. [https://doi.org/10.1007/s12282-012-0394-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22968626 PubMed]
 
−
# Toi M, Imoto S, Ishida T, Ito Y, Iwata H, Masuda N, Mukai H, Saji S, Shimizu A, Ikeda T, Haga H, Saeki T, Aogi K, Sugie T, Ueno T, Kinoshita T, Kai Y, Kitada M, Sato Y, Jimbo K, Sato N, Ishiguro H, Takada M, Ohashi Y, Ohno S. Adjuvant S-1 plus endocrine therapy for oestrogen receptor-positive, HER2-negative, primary breast cancer: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):74-84. [https://doi.org/10.1016/s1470-2045(20)30534-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33387497 PubMed] UMIN000003969
 
−
=Metastatic disease, first-line therapy, premenopausal=
 
−
==Anastrozole & Goserelin {{#subobject:796eey|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bxo33c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole.2C_Goserelin.2C_Ribociclib|Anastrozole, Goserelin, Ribociclib]]<br>2. [[#Goserelin.2C_Letrozole.2C_Ribociclib|Goserelin, Letrozole, Ribociclib]]<br>3. [[#Goserelin.2C_Ribociclib.2C_Tamoxifen|Goserelin, Ribociclib, Tamoxifen]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Anastrozole, Goserelin, Ribociclib {{#subobject:443971|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d9afb9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Anastrozole_.26_Goserelin|Anastrozole & Goserelin]]<br>2. [[#Goserelin_.26_Letrozole|Goserelin & Letrozole]]<br>3. [[#Goserelin_.26_Tamoxifen_3|Goserelin & Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 58.7 vs 48 mo<br>(HR 0.76, 95% CI 0.61-0.96)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Goserelin & Letrozole {{#subobject:75uh11|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d7ef99|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole.2C_Goserelin.2C_Ribociclib|Anastrozole, Goserelin, Ribociclib]]<br>2. [[#Goserelin.2C_Letrozole.2C_Ribociclib|Goserelin, Letrozole, Ribociclib]]<br>3. [[#Goserelin.2C_Ribociclib.2C_Tamoxifen|Goserelin, Ribociclib, Tamoxifen]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Goserelin, Letrozole, Ribociclib {{#subobject:b2mx78|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:pb1f2e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Anastrozole_.26_Goserelin|Anastrozole & Goserelin]]<br>2. [[#Goserelin_.26_Letrozole|Goserelin & Letrozole]]<br>3. [[#Goserelin_.26_Tamoxifen_3|Goserelin & Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 58.7 vs 48 mo<br>(HR 0.76, 95% CI 0.61-0.96)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Goserelin, Ribociclib, Tamoxifen {{#subobject:93f428|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e86701|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Anastrozole_.26_Goserelin|Anastrozole & Goserelin]]<br>2. [[#Goserelin_.26_Letrozole|Goserelin & Letrozole]]<br>3. [[#Goserelin_.26_Tamoxifen_3|Goserelin & Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 58.7 vs 48 mo<br>(HR 0.76, 95% CI 0.61-0.96)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Goserelin & Tamoxifen {{#subobject:dffau3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:hcxj965|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30292-4 Tripathy et al. 2018 (MONALEESA-7)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole.2C_Goserelin.2C_Ribociclib|Anastrozole, Goserelin, Ribociclib]]<br>2. [[#Goserelin.2C_Letrozole.2C_Ribociclib|Goserelin, Letrozole, Ribociclib]]<br>3. [[#Goserelin.2C_Ribociclib.2C_Tamoxifen|Goserelin, Ribociclib, Tamoxifen]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 [http://www.abstracts2view.com/sabcs/view.php?nu=SABCS17L_828 link to abstract] '''contains dosing details in abstract''' -->
 
−
# '''MONALEESA-7:''' Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. Epub 2018 May 24. [https://doi.org/10.1016/S1470-2045(18)30292-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29804902 PubMed] NCT02278120
 
−
##'''Update:''' Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. [https://doi.org/10.1158/1078-0432.ccr-21-3032 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34965945/ PubMed]
 
−
==Tamoxifen monotherapy {{#subobject:dh71bb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20 mg/day {{#subobject:4979xq|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1986.4.2.178 Ingle et al. 1986a]
 
−
|1978-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Endocrine_ablation_surgery#Bilateral_oophorectomy_88|Bilateral oophorectomy]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
**Some earlier trials used 10 mg PO twice per day instead
 
−
'''Continued indefinitely'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 40 mg/day {{#subobject:4jj1bb5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1986.4.9.1326 Buchanan et al. 1986]
 
−
|1979-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Endocrine_ablation_surgery#Bilateral_oophorectomy_88|Bilateral oophorectomy]]
 
−
| style="background-color:#d9ef8b" |Might have superior PFS
 
−
|-
 
−
|[https://doi.org/10.1023/a:1005833811584 Crump et al. 1997]
 
−
|NR
 
−
|style="background-color:#1a9851" |Randomized (E-RT-switch-ic)
 
−
|[[Endocrine_ablation_surgery#Bilateral_oophorectomy_88|Bilateral oophorectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet pooled endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: while Crump et al. 1997 is a meta-analysis, it is also the primary report for a randomized trial used to support registration of this drug.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 40 mg PO once per day
 
−
**Some earlier trials used 20 mg PO twice per day instead
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Ingle JN, Krook JE, Green SJ, Kubista TP, Everson LK, Ahmann DL, Chang MN, Bisel HF, Windschitl HE, Twito DI, Pfeifle DM. Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J Clin Oncol. 1986 Feb;4(2):178-85. [https://doi.org/10.1200/JCO.1986.4.2.178 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3511184 PubMed]
 
−
# Buchanan RB, Blamey RW, Durrant KR, Howell A, Paterson AG, Preece PE, Smith DC, Williams CJ, Wilson RG. A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J Clin Oncol. 1986 Sep;4(9):1326-30. [https://doi.org/10.1200/JCO.1986.4.9.1326 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3528402 PubMed]
 
−
# Crump M, Sawka CA, DeBoer G, Buchanan RB, Ingle JN, Forbes J, Meakin JW, Shelley W, Pritchard KI. An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer. Breast Cancer Res Treat. 1997 Jul;44(3):201-10. [https://doi.org/10.1023/a:1005833811584 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9266099 PubMed]
 
−
=Metastatic disease, first-line therapy=
 
−
==Abemaciclib & Anastrozole {{#subobject:213a4e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c0e636|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Anastrozole_monotherapy_3|Anastrozole]]<br>2. [[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 14.7 mo<br>(HR 0.54, 95% CI 0.41-0.72)
 
−
|-
 
−
|}
 
−
====Targeted therapy====
 
−
*[[Abemaciclib (Verzenio)]] 150 mg PO twice per day
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONARCH 3:''' Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.75.6155 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28968163 PubMed] NCT02246621
 
−
==Abemaciclib & Letrozole {{#subobject:cb27ef|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e434e3|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Anastrozole_monotherapy_3|Anastrozole]]<br>2. [[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 14.7 mo<br>(HR 0.54, 95% CI 0.41-0.72)
 
−
|-
 
−
|}
 
−
====Targeted therapy====
 
−
*[[Abemaciclib (Verzenio)]] 150 mg PO twice per day
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONARCH 3:''' Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.75.6155 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28968163 PubMed] NCT02246621
 
−
==Anastrozole monotherapy {{#subobject:796bb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bd033c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.22.3748 Bonneterre et al. 2000 (TARGET<sub>Breast</sub>)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#eeee01" |Equivalent TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.22.3758 Nabholtz et al. 2000 (Arimidex Study Group 2000)]
 
−
|1996-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|[https://insights.ovid.com/pubmed?pmid=12796608 Milla-Santos et al. 2003]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.38.1095 Bergh et al. 2012 (FACT)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_.26_Fulvestrant|Anastrozole & Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ Mehta et al. 2012 (SWOG S0226)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_.26_Fulvestrant|Anastrozole & Fulvestrant]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669502/ Iwata et al. 2013 (A5991048)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_monotherapy_3|Exemestane]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(16)32389-3 Robertson et al. 2016 (FALCON)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Abemaciclib_.26_Anastrozole|Abemaciclib & Anastrozole]]<br>2. [[#Abemaciclib_.26_Letrozole|Abemaciclib & Letrozole]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''TARGET<sub>Breast</sub>:''' Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M, von Euler M. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000 Nov 15;18(22):3748-57. Erratum in: J Clin Oncol. 2012 Jan 20;30(3):343. [https://doi.org/10.1200/JCO.2000.18.22.3748 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11078487 PubMed]
 
−
# '''Arimidex Study Group 2000:''' Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial; Arimidex Study Group. J Clin Oncol. 2000 Nov 15;18(22):3758-67. [https://doi.org/10.1200/JCO.2000.18.22.3758 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11078488 PubMed]
 
−
# Milla-Santos A, Milla L, Portella J, Rallo L, Pons M, Rodes E, Casanovas J, Puig-Gali M. Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer: a prospective, randomized, phase III study. Am J Clin Oncol. 2003 Jun;26(3):317-22. [https://insights.ovid.com/pubmed?pmid=12796608 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12796608 PubMed]
 
−
# '''FACT:''' Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. [https://doi.org/10.1200/JCO.2011.38.1095 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22370325 PubMed] NCT00256698
 
−
# '''SWOG S0226:''' Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. [https://doi.org/10.1056/NEJMoa1201622 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22853014 PubMed] NCT00075764
 
−
## '''Update:''' Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Linden HH, Livingston RB, Hortobagyi GN. Overall survival with fulvestrant plus anastrozole in metastatic breast cancer. N Engl J Med. 2019 Mar 28;380(13):1226-1234. Erratum in: N Engl J Med. 2019 Jun 6;380(23):2282. [https://doi.org/10.1056/NEJMoa1811714 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30917258 PubMed]
 
−
# '''A5991048:''' Iwata H, Masuda N, Ohno S, Rai Y, Sato Y, Ohsumi S, Hashigaki S, Nishizawa Y, Hiraoka M, Morimoto T, Sasano H, Saeki T, Noguchi S. A randomized, double-blind, controlled study of exemestane versus anastrozole for the first-line treatment of postmenopausal Japanese women with hormone-receptor-positive advanced breast cancer. Breast Cancer Res Treat. 2013 Jun;139(2):441-51. Epub 2013 May 30. [https://doi.org/10.1007/s10549-013-2573-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669502/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23715630 PubMed] NCT00143390
 
−
# '''FALCON:''' Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. [https://doi.org/10.1016/S0140-6736(16)32389-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27908454 PubMed] NCT01602380
 
−
# '''MONARCH-3:''' Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.75.6155 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28968163 PubMed] NCT02246621
 
−
# '''DAWNA-2:''' NCT03966898
 
−
==Anastrozole & Fulvestrant {{#subobject:c3bc6e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7ef8ed|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.38.1095 Bergh et al. 2012 (FACT)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ Mehta et al. 2012 (SWOG S0226)]
 
−
|2004-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 47.7 vs 41.3 mo<br>(HR 0.81, 95% CI 0.65-1.00)
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once on day 1, then 250 mg IM once on day 15
 
−
**Cycle 2 onwards: 250 mg IM once on day 1
 
−
***Patients in '''SWOG S0226''' who progressed while on therapy were allowed to receive a higher dose, 500 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''FACT:''' Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. [https://doi.org/10.1200/JCO.2011.38.1095 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22370325 PubMed] NCT00256698
 
−
# '''SWOG S0226:''' Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. [https://doi.org/10.1056/NEJMoa1201622 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951300/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22853014 PubMed] NCT00075764
 
−
## '''Update:''' Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Linden HH, Livingston RB, Hortobagyi GN. Overall survival with fulvestrant plus anastrozole in metastatic breast cancer. N Engl J Med. 2019 Mar 28;380(13):1226-1234. Erratum in: N Engl J Med. 2019 Jun 6;380(23):2282. [https://doi.org/10.1056/NEJMoa1811714 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30917258 PubMed]
 
−
==Exemestane monotherapy {{#subobject:d17b4d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:babfaa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652082/ Paridaens et al. 2008 (EORTC 10951)]
 
−
|1996-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1007/s10549-008-0229-5 Falandry et al. 2008 (CELAROM)]
 
−
|2003-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Celecoxib_.26_Exemestane_99|Celecoxib & Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669502/ Iwata et al. 2013 (A5991048)]
 
−
|2005-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior TTP
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''EORTC 10951:''' Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T, Piccart MJ, Bogaerts J, Therasse P; European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008 Oct 20;26(30):4883-90. Epub 2008 Sep 15. [https://doi.org/10.1200/JCO.2007.14.4659 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652082/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18794551 PubMed] NCT00002777
 
−
# '''CELAROM:''' Falandry C, Debled M, Bachelot T, Delozier T, Crétin J, Romestaing P, Mille D, You B, Mauriac L, Pujade-Lauraine E, Freyer G. Celecoxib and exemestane versus placebo and exemestane in postmenopausal metastatic breast cancer patients: a double-blind phase III GINECO study. Breast Cancer Res Treat. 2009 Aug;116(3):501-8. Epub 2008 Nov 20. [https://doi.org/10.1007/s10549-008-0229-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19020973 PubMed] NCT00525096
 
−
# '''A5991048:''' Iwata H, Masuda N, Ohno S, Rai Y, Sato Y, Ohsumi S, Hashigaki S, Nishizawa Y, Hiraoka M, Morimoto T, Sasano H, Saeki T, Noguchi S. A randomized, double-blind, controlled study of exemestane versus anastrozole for the first-line treatment of postmenopausal Japanese women with hormone-receptor-positive advanced breast cancer. Breast Cancer Res Treat. 2013 Jun;139(2):441-51. Epub 2013 May 30. [https://doi.org/10.1007/s10549-013-2573-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669502/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23715630 PubMed] NCT00143390
 
−
==Fulvestrant monotherapy {{#subobject:da9e37|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 250 mg {{#subobject:addae5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2014.57.2388 Martín et al. 2015 (LEA)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Bevacizumab_99|Fulvestrant & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] 250 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 500 mg {{#subobject:e6f584|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.02.112 Howell et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(16)32389-3 Robertson et al. 2016 (FALCON)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 16.6 vs 13.8 mo<br>(HR 0.80, 95% CI 0.64-0.999)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.78.9909 Slamon et al. 2018 (MONALEESA-3)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Ribociclib|Fulvestrant & Ribociclib]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for MONALEESA-3 is based on the 2021 update.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. [https://doi.org/10.1200/jco.2004.02.112 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15117982 PubMed]
 
−
# '''LEA:''' Martín M, Loibl S, von Minckwitz G, Morales S, Martinez N, Guerrero A, Anton A, Aktas B, Schoenegg W, Muñoz M, Garcia-Saenz JÁ, Gil M, Ramos M, Margeli M, Carrasco E, Liedtke C, Wachsmann G, Mehta K, de la Haba-Rodríguez J. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015 Mar 20;33(9):1045-52. Epub 2015 Feb 17. [https://doi.org/10.1200/JCO.2014.57.2388 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25691671 PubMed] NCT00545077
 
−
# '''FALCON:''' Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. [https://doi.org/10.1016/S0140-6736(16)32389-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27908454 PubMed] NCT01602380
 
−
# '''MONALEESA-3:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. Epub 2018 Jun 3. [https://doi.org/10.1200/JCO.2018.78.9909 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29860922 PubMed] NCT02422615
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. Epub 2019 Dec 11. [https://doi.org/10.1056/NEJMoa1911149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31826360 PubMed]
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. Epub 2021 Jun 5. Erratum in: Ann Oncol. 2021 Oct;32(10):1307. [https://doi.org/10.1016/j.annonc.2021.05.353 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34102253/ PubMed]
 
−
==Fulvestrant & Ribociclib {{#subobject:f6031e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:310fb1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.78.9909 Slamon et al. 2018 (MONALEESA-3)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 53.7 vs 41.5 mo<br>(HR 0.73, 95% CI 0.59-0.90)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONALEESA-3:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. Epub 2018 Jun 3. [https://doi.org/10.1200/JCO.2018.78.9909 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29860922 PubMed] NCT02422615
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. Epub 2019 Dec 11. [https://doi.org/10.1056/NEJMoa1911149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31826360 PubMed]
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. Epub 2021 Jun 5. Erratum in: Ann Oncol. 2021 Oct;32(10):1307. [https://doi.org/10.1016/j.annonc.2021.05.353 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34102253/ PubMed]
 
−
==Goserelin monotherapy {{#subobject:53b67a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:gga26c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(94)00415-2/pdf Jonat et al. 1995]
 
−
|1988-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Goserelin_.26_Tamoxifen_3|Goserelin & Tamoxifen]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]]
 
−
</div></div>
 
−
===References===
 
−
# Jonat W, Kaufmann M, Blamey RW, Howell A, Collins JP, Coates A, Eiermann W, Jänicke F, Njordenskold B, Forbes JF, Kolvenbag GJCM. A randomised study to compare the effect of the luteinising hormone releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and perimenopausal patients with advanced breast cancer. Eur J Cancer. 1995;31A(2):137-42. [https://www.ejcancer.com/article/0959-8049(94)00415-2/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/7718316 PubMed]
 
−
==Goserelin & Tamoxifen {{#subobject:46ef1e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:644f0d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(94)00415-2/pdf Jonat et al. 1995]
 
−
|1988-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Goserelin_monotherapy_2|Goserelin]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Goserelin (Zoladex)]]
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
</div></div>
 
−
===References===
 
−
# Jonat W, Kaufmann M, Blamey RW, Howell A, Collins JP, Coates A, Eiermann W, Jänicke F, Njordenskold B, Forbes JF, Kolvenbag GJCM. A randomised study to compare the effect of the luteinising hormone releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and perimenopausal patients with advanced breast cancer. Eur J Cancer. 1995;31A(2):137-42. [https://www.ejcancer.com/article/0959-8049(94)00415-2/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/7718316 PubMed]
 
−
==Letrozole monotherapy {{#subobject:75d541|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d7ef99|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.10.2596 Mouridsen et al. 2001 (ILBCG)]
 
−
|1996-1999
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.09.5455 Goss et al. 2007 (Biomed 777-CLP-29)]
 
−
|2002-2005
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Atamestane_.26_Toremifene_77|Atamestane & Toremifene]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532391/ Wolff et al. 2012 (HORIZON<sub>BRCA</sub>)]
 
−
|2004-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_.26_Temsirolimus_99|Letrozole & Temsirolimus]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2014.57.2388 Martín et al. 2015 (LEA)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_.26_Bevacizumab|Letrozole & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ Dickler et al. 2016 (CALGB 40503)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_.26_Bevacizumab|Letrozole & Bevacizumab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2814%2971159-3 Finn et al. 2015 (PALOMA-1/TRIO-18)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Letrozole_.26_Palbociclib|Letrozole & Palbociclib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1607303 Finn et al. 2016 (PALOMA-2)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_.26_Palbociclib|Letrozole & Palbociclib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1609709 Hortobagyi et al. 2016 (MONALEESA-2)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_.26_Ribociclib|Letrozole & Ribociclib]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.75.6155 Goetz et al. 2017 (MONARCH 3)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Abemaciclib_.26_Anastrozole|Abemaciclib & Anastrozole]]<br>2. [[#Abemaciclib_.26_Letrozole|Abemaciclib & Letrozole]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''<br>
 
−
''Note: HORIZON is labeled HORIZON<sub>BRCA</sub> to distinguish from the study of the same name in multiple myeloma.''
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ILBCG:''' Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol. 2001 May 15;19(10):2596-606. Erratum in: J Clin Oncol 2001 Jul 1;19(13):3302. [https://doi.org/10.1200/JCO.2001.19.10.2596 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11352951 PubMed]
 
−
## '''Update:''' Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Chaudri-Ross H, Lang R, Wyld P, Bhatnagar A. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003 Jun 1;21(11):2101-9. [https://doi.org/10.1200/JCO.2003.04.194 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12775735 PubMed]
 
−
# '''Biomed 777-CLP-29:''' Goss P, Bondarenko IN, Manikhas GN, Pendergrass KB, Miller WH Jr, Langecker P, Blanchett D. Phase III, double-blind, controlled trial of atamestane plus toremifene compared with letrozole in postmenopausal women with advanced receptor-positive breast cancer. J Clin Oncol. 2007 Nov 1;25(31):4961-6. [https://doi.org/10.1200/JCO.2006.09.5455 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17971594 PubMed] NCT00044291
 
−
# '''HORIZON<sub>BRCA</sub>:''' Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, Sun Y, Neskovic-Konstantinovic Z, Guimaraes RC, Fumoleau P, Chan A, Hachemi S, Strahs A, Cincotta M, Berkenblit A, Krygowski M, Kang LL, Moore L, Hayes DF. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013 Jan 10;31(2):195-202. Epub 2012 Dec 10. [https://doi.org/10.1200/JCO.2011.38.3331 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532391/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23233719 PubMed] NCT00083993
 
−
# '''PALOMA-1/TRIO-18:''' Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. [https://doi.org/10.1016/S1470-2045%2814%2971159-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25524798 PubMed] NCT00721409
 
−
# '''LEA:''' Martín M, Loibl S, von Minckwitz G, Morales S, Martinez N, Guerrero A, Anton A, Aktas B, Schoenegg W, Muñoz M, Garcia-Saenz JÁ, Gil M, Ramos M, Margeli M, Carrasco E, Liedtke C, Wachsmann G, Mehta K, de la Haba-Rodríguez J. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015 Mar 20;33(9):1045-52. Epub 2015 Feb 17. [https://doi.org/10.1200/JCO.2014.57.2388 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25691671 PubMed] NCT00545077
 
−
<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
 
−
# '''CALGB 40503:''' Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016 Aug 1;34(22):2602-9. Epub 2016 May 2. [https://doi.org/10.1200/jco.2015.66.1595 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27138575 PubMed] NCT00601900
 
−
# '''MONALEESA-2:''' Hortobagyi GN, Stemmer SM, Burris HA 3rd, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7.[https://doi.org/10.1056/NEJMoa1609709 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27717303 PubMed] NCT01958021
 
−
## '''Subgroup analysis:''' Sonke GS, Hart LL, Campone M, Erdkamp F, Janni W, Verma S, Villanueva C, Jakobsen E, Alba E, Wist E, Favret AM, Bachelot T, Hegg R, Wheatley-Price P, Souami F, Sutradhar S, Miller M, Germa C, Burris HA. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat. 2018 Feb;167(3):659-669. Epub 2017 Oct 22. [https://doi.org/10.1007/s10549-017-4523-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807486/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29058175 PubMed]
 
−
## '''HRQoL analysis:''' Verma S, O'Shaughnessy J, Burris HA, Campone M, Alba E, Chandiwana D, Dalal AA, Sutradhar S, Monaco M, Janni W. Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Breast Cancer Res Treat. 2018 Aug;170(3):535-545. Epub 2018 Apr 13. [https://doi.org/10.1007/s10549-018-4769-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29654415 PubMed]
 
−
## '''Update:''' Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018 Jul 1;29(7):1541-1547. [https://doi.org/10.1093/annonc/mdy155 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29718092 PubMed]
 
−
##'''Update:''' Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022 Mar 10;386(10):942-950. [https://doi.org/10.1056/nejmoa2114663 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35263519/ PubMed]
 
−
# '''PALOMA-2:''' Finn RS, Martín M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. [https://doi.org/10.1056/NEJMoa1607303 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27959613 PubMed] NCT01740427
 
−
## '''Update:''' Rugo HS, Finn RS, Diéras V, Ettl J, Lipatov O, Joy AA, Harbeck N, Castrellon A, Iyer S, Lu DR, Mori A, Gauthier ER, Bartlett CH, Gelmon KA, Slamon DJ. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019 Apr;174(3):719-729. Epub 2019 Jan 10. [https://doi.org/10.1007/s10549-018-05125-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30632023 PubMed]
 
−
## '''Subgroup analysis:''' Im SA, Mukai H, Park IH, Masuda N, Shimizu C, Kim SB, Im YH, Ohtani S, Huang Bartlett C, Lu DR, Iyer S, Mori Y, Mori A, Gauthier E, Finn RS, Toi M. Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. J Glob Oncol. 2019 May;5:1-19. [https://doi.org/10.1200/jgo.18.00173 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6550032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31125276 PubMed]
 
−
# '''MONARCH 3:''' Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.75.6155 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28968163 PubMed] NCT02246621
 
−
# '''DAWNA-2:''' NCT03966898
 
−
==Letrozole & Bevacizumab {{#subobject:86d541|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d7fg12|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2014.57.2388 Martín et al. 2015 (LEA)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 19.3 vs 14.4 mo<br>(HR 0.83, 95% CI 0.65-1.06)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ Dickler et al. 2016 (CALGB 40503)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 20.2 vs 15.6 mo<br>(HR 0.75, 95% CI 0.59-0.96)
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''LEA:''' Martín M, Loibl S, von Minckwitz G, Morales S, Martinez N, Guerrero A, Anton A, Aktas B, Schoenegg W, Muñoz M, Garcia-Saenz JÁ, Gil M, Ramos M, Margeli M, Carrasco E, Liedtke C, Wachsmann G, Mehta K, de la Haba-Rodríguez J. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015 Mar 20;33(9):1045-52. Epub 2015 Feb 17. [https://doi.org/10.1200/JCO.2014.57.2388 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25691671 PubMed] NCT00545077
 
−
<!-- Presented in part at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015. -->
 
−
# '''CALGB 40503:''' Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016 Aug 1;34(22):2602-9. Epub 2016 May 2. [https://doi.org/10.1200/jco.2015.66.1595 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012690/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27138575 PubMed] NCT00601900
 
−
==Letrozole & Palbociclib {{#subobject:da6f2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d4d90|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2814%2971159-3 Finn et al. 2015 (PALOMA-1/TRIO-18)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 20.2 vs 10.2 mo<br>(HR 0.49, 95% CI 0.32-0.75)
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1607303 Finn et al. 2016 (PALOMA-2)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 24.8 vs 14.5 mo<br>(HR 0.58, 95% CI 0.46-0.72)
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Palbociclib (Ibrance)]] 125 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PALOMA-1/TRIO-18:''' Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. [https://doi.org/10.1016/S1470-2045%2814%2971159-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25524798 PubMed] NCT00721409
 
−
# '''PALOMA-2:''' Finn RS, Martín M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. [https://doi.org/10.1056/NEJMoa1607303 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27959613 PubMed] NCT01740427
 
−
## '''Update:''' Rugo HS, Finn RS, Diéras V, Ettl J, Lipatov O, Joy AA, Harbeck N, Castrellon A, Iyer S, Lu DR, Mori A, Gauthier ER, Bartlett CH, Gelmon KA, Slamon DJ. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019 Apr;174(3):719-729. Epub 2019 Jan 10. [https://doi.org/10.1007/s10549-018-05125-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30632023 PubMed]
 
−
## '''Subgroup analysis:''' Im SA, Mukai H, Park IH, Masuda N, Shimizu C, Kim SB, Im YH, Ohtani S, Huang Bartlett C, Lu DR, Iyer S, Mori Y, Mori A, Gauthier E, Finn RS, Toi M. Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. J Glob Oncol. 2019 May;5:1-19. [https://doi.org/10.1200/jgo.18.00173 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6550032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31125276 PubMed]
 
−
==Letrozole & Ribociclib {{#subobject:b27d88|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:66fc2e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1609709 Hortobagyi et al. 2016 (MONALEESA-2)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 63.9 vs 51.4 mo<br>(HR 0.76, 95% CI 0.63-0.93)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONALEESA-2:''' Hortobagyi GN, Stemmer SM, Burris HA 3rd, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7. [https://doi.org/10.1056/NEJMoa1609709 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27717303 PubMed] NCT01958021
 
−
## '''Subgroup analysis:''' Sonke GS, Hart LL, Campone M, Erdkamp F, Janni W, Verma S, Villanueva C, Jakobsen E, Alba E, Wist E, Favret AM, Bachelot T, Hegg R, Wheatley-Price P, Souami F, Sutradhar S, Miller M, Germa C, Burris HA. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat. 2018 Feb;167(3):659-669. Epub 2017 Oct 22. [https://doi.org/10.1007/s10549-017-4523-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807486/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29058175 PubMed]
 
−
## '''HRQoL analysis:''' Verma S, O'Shaughnessy J, Burris HA, Campone M, Alba E, Chandiwana D, Dalal AA, Sutradhar S, Monaco M, Janni W. Health-related quality of life of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with ribociclib + letrozole: results from MONALEESA-2. Breast Cancer Res Treat. 2018 Aug;170(3):535-545. Epub 2018 Apr 13. [https://doi.org/10.1007/s10549-018-4769-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29654415 PubMed]
 
−
## '''Update:''' Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018 Jul 1;29(7):1541-1547. [https://doi.org/10.1093/annonc/mdy155 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29718092 PubMed]
 
−
##'''Update:''' Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022 Mar 10;386(10):942-950. [https://doi.org/10.1056/nejmoa2114663 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35263519/ PubMed]
 
−
==Tamoxifen monotherapy {{#subobject:dffabd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 20 mg/day {{#subobject:497965|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198101013040104 Ingle et al. 1981]
 
−
|1977-1980
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer_-_historical#DES_monotherapy|DES]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J Gale et al. 1994]
 
−
|1977-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Breast_cancer_-_historical#Aminoglutethimide_monotherapy|Aminoglutethimide]]<br> 2. [[Endocrine_ablation_surgery#Bilateral_adrenalectomy_88|Bilateral adrenalectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DOR/TTF/OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)91872-5 Powles et al. 1984]
 
−
|1979-1983
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#TAD_.28Tamoxifen.29|TAD]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976875/ Bratherton et al. 1984]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]; 40 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1986.4.6.958 Ingle et al. 1986]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethemide.2C_Hydrocortisone.2C_Tamoxifen_99|Aminoglutethemide, Hydrocortisone, Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.7.1098 Muss et al. 1988]
 
−
|1981-1984
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.5.825 Ingle et al. 1988]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fluoxymesterone_.26_Tamoxifen_77|Fluoxymesterone & Tamoxifen]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP<sup>1</sup>
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246832/ Rubens et al. 1988]
 
−
|1981-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_Prednisolone|Tamoxifen & Prednisolone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058657 Castiglione-Gertsch et al. 1993]
 
−
|1982-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#Medroxyprogesterone_monotherapy|MPA]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(88)91478-X Gazet et al. 1988]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Surgery
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1994.12.10.2071 Borner et al. 1994 (SAKK 23/82)]
 
−
|1982-1991
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_88|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<sup>2</sup>
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf Stuart et al. 1996]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19910701)68:1%3C34::AID-CNCR2820680107%3E3.0.CO;2-Q Ingle et al. 1991]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen_.26_Prednisolone|Tamoxifen & Prednisolone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1994.12.8.1630 Muss et al. 1994]
 
−
|1985-1990
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#Medroxyprogesterone_monotherapy|MPA]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.1995.13.10.2556 Hayes et al. 1995]
 
−
| rowspan="2" |1988-1991
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Toremifene_monotherapy_2|Toremifene]]; 60 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|2. [[#Toremifene_monotherapy_2|Toremifene]]; 200 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a010635 Thürlimann et al. 1996 (SAKK 20/88)]
 
−
|1988-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fadrozole_monotherapy_77|Fadrozole]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTTF
 
−
|-
 
−
|[https://doi.org/10.1023/a:1015229630260 Buzdar et al. 2002]
 
−
|1995-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Droloxifene_monotherapy_77|Droloxifene]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.22.3748 Bonneterre et al. 2000 (TARGET<sub>Breast</sub>)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#eeee01" |Equivalent TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.22.3758 Nabholtz et al. 2000 (Arimidex Study Group 2000)]
 
−
|1996-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.10239 Bajetta et al. 2002]
 
−
|1996-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Octreotide_LAR_.26_Tamoxifen_99|Octreotide LAR & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.10.2596 Mouridsen et al. 2001 (ILBCG)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Letrozole_monotherapy_3|Letrozole]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652082/ Paridaens et al. 2008 (EORTC 10951)]
 
−
|1996-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_monotherapy_3|Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.02.112 Howell et al. 2004]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy|Fulvestrant]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.09.5992 Deshmane et al. 2007]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Arzoxifene_monotherapy_77|Arzoxifene]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Ingle et al. 1988 is based on the 1991 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for SAKK 23/82 is based on the 2003 update.''<br>
 
−
''Note: patients in Gazet et al. 1988 had resectable disease but did not undergo surgery in this arm. Patients in SAKK 23/82 had isolated locoregional recurrence.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
**Some earlier trials used 10 mg PO twice per day instead
 
−
'''28-day cycles'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 30 mg/day {{#subobject:de3bbg|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/BF01812683 Gundersen et al. 1990a]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tamoxifen.2FMPA_88|Tamoxifen/MPA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 30 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 40 mg/day {{#subobject:de3aaf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/191185 Morgan et al. 1976]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://annals.org/aim/fullarticle/691616/tamoxifen-antiestrogen-therapy-advanced-breast-cancer Kiang et al. 1977]
 
−
|1975-1976
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976875/ Bratherton et al. 1984]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]; 20 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1986.4.2.186 Forbes 1986]
 
−
|1978-1981
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|AC]]<br> 2. [[#ACT_99|ACT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19871115)60:10%3C2376::AID-CNCR2820601005%3E3.0.CO;2-N Kellokumpu-Lehtinen et al. 1987]
 
−
|1979-1983
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Nandrolone_monotherapy_99|Nandrolone]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 van Veelen et al. 1986]
 
−
|1980-1984
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer_-_historical#Medroxyprogesterone_monotherapy|MPA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058658 Gill et al. 1993]
 
−
|1984-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]<br>2. [[#Megestrol_.26_Tamoxifen_99|Megestrol & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ Pyrhönen et al. 1997]
 
−
|1986-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Toremifene_monotherapy_2|Toremifene]]; 60 mg/day
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1023/a:1005891506092 Gershanovich et al. 1997]
 
−
| rowspan="2" |1987-1992
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Toremifene_monotherapy_2|Toremifene]]; 60 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP
 
−
|-
 
−
|2. [[#Toremifene_monotherapy_2|Toremifene]]; 240 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(06)00765-9 Beex et al. 2006 (EORTC 10863)]
 
−
|1987-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Tamoxifen_monotherapy_4|Tamoxifen]]; intermittent<br>2. [[#Tamoxifen.2FMPA_99|Tamoxifen/MPA]]; intermittent
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1023/a:1006440802709 Milla-Santos et al. 2001]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Toremifene_monotherapy_2|Toremifene]]; 60 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP/OS
 
−
|-
 
−
|[https://insights.ovid.com/pubmed?pmid=12796608 Milla-Santos et al. 2003]
 
−
|1997-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Anastrozole_monotherapy_3|Anastrozole]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 40 mg PO once per day
 
−
**Some earlier trials used 20 mg PO twice per day instead
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Morgan LR Jr, Schein PS, Woolley PV, Hoth D, Macdonald J, Lippman M, Posey LE, Beazley RW. Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. Cancer Treat Rep. 1976 Oct;60(10):1437-43. [https://pubmed.ncbi.nlm.nih.gov/191185 PubMed]
 
−
# Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann Intern Med. 1977 Dec;87(6):687-90. [http://annals.org/aim/fullarticle/691616/tamoxifen-antiestrogen-therapy-advanced-breast-cancer link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/931204 PubMed]
 
−
# Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. [https://doi.org/10.1056/NEJM198101013040104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7001242 PubMed]
 
−
# Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. [https://doi.org/10.1016/S0140-6736(84)91872-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6145832 PubMed]
 
−
# Bratherton DG, Brown CH, Buchanan R, Hall V, Kingsley Pillers EM, Wheeler TK, Williams CJ. A comparison of two doses of tamoxifen (Nolvadex) in postmenopausal women with advanced breast cancer: 10 mg bd versus 20 mg bd. Br J Cancer. 1984 Aug;50(2):199-205. [https://doi.org/10.1038/bjc.1984.163 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976875/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/6380554 PubMed]
 
−
# Forbes JF; Australian and New Zealand Breast Cancer Trials Group. A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. J Clin Oncol. 1986 Feb;4(2):186-93. [https://doi.org/10.1200/JCO.1986.4.2.186 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2868074 PubMed]
 
−
# Ingle JN, Green SJ, Ahmann DL, Long HJ, Edmonson JH, Rubin J, Chang MN, Creagan ET. Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer. J Clin Oncol. 1986 Jun;4(6):958-64. [https://doi.org/10.1200/JCO.1986.4.6.958 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3519885 PubMed]
 
−
# van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. [https://doi.org/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2939943 PubMed]
 
−
# Kellokumpu-Lehtinen P, Huovinen R, Johansson R. Hormonal treatment of advanced breast cancer: a randomized trial of tamoxifen versus nandrolone decanoate. Cancer. 1987 Nov 15;60(10):2376-81. [https://doi.org/10.1002/1097-0142(19871115)60:10%3C2376::AID-CNCR2820601005%3E3.0.CO;2-N link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3664426 PubMed]
 
−
# Gazet JC, Markopoulos C, Ford HT, Coombes RC, Bland JM, Dixon RC. Prospective randomised trial of tamoxifen versus surgery in elderly patients with breast cancer. Lancet. 1988 Mar 26;1(8587):679-81. [https://doi.org/10.1016/S0140-6736(88)91478-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/2895214 PubMed]
 
−
# Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Marschke RF, Long HJ, Gerstner JG, Windschitl HE, Everson LK, Pfeifle DM. Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer. J Clin Oncol. 1988 May;6(5):825-31. [https://doi.org/10.1200/JCO.1988.6.5.825 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3284975 PubMed]
 
−
## '''Update:''' Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Tschetter LK, Long HJ, Gerstner JG, Windschitl HE, Levitt R, Pfeifle DM. Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer: an updated analysis. Cancer. 1991 Feb 15;67(4):886-91. [https://doi.org/10.1002/1097-0142(19910215)67:4%3C886::AID-CNCR2820670405%3E3.0.CO;2-O link to original article] [https://pubmed.ncbi.nlm.nih.gov/1991261 PubMed]
 
−
# Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. [https://doi.org/10.1200/JCO.1988.6.7.1098 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3292710 PubMed]
 
−
# Rubens RD, Tinson CL, Coleman RE, Knight RK, Tong D, Winter PJ, North WR. Prednisolone improves the response to primary endocrine treatment for advanced breast cancer. Br J Cancer. 1988 Nov;58(5):626-30. [https://doi.org/10.1038/bjc.1988.273 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246832/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3219274 PubMed]
 
−
# Gundersen S, Kvinnsland S, Lundgren S, Klepp O, Lund E, Børmer O, Høst H. Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer. Breast Cancer Res Treat. 1990 Nov;17(1):45-50. [https://doi.org/10.1007/BF01812683 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2151369 PubMed]
 
−
# Ingle JN, Mailliard JA, Schaid DJ, Krook JE, Gesme DH Jr, Windschitl HE, Pfeifle DM, Etzell PS, Gerstner JG, Long HJ, Foley JF, Loprinzi CL, Dalton RJ; NCCTG. A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer: a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. Cancer. 1991 Jul 1;68(1):34-9. [https://doi.org/10.1002/1097-0142(19910701)68:1%3C34::AID-CNCR2820680107%3E3.0.CO;2-Q link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2049750 PubMed]
 
−
# Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. [https://doi.org/10.1093/oxfordjournals.annonc.a058657 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8280653 PubMed]
 
−
# Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. [https://doi.org/10.1093/oxfordjournals.annonc.a058658 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8280654 PubMed]
 
−
# Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ; Eastern Cooperative Oncology Group. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. [https://doi.org/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J link to original article] [https://pubmed.ncbi.nlm.nih.gov/8293400 PubMed]
 
−
# Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, Spurr CL, Eagle K, White DR. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. [https://doi.org/10.1200/JCO.1994.12.8.1630 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8040675 PubMed]
 
−
# '''SAKK 23/82:''' Borner M, Bacchi M, Goldhirsch A, Greiner R, Harder F, Castiglione M, Jungi WF, Thürlimann B, Cavalli F, Obrecht JP, Leyvraz S, Alberto P, Adam H, Varini M, Loehnert T, Senn HJ, Metzger U, Brunner K; Swiss Group for Clinical Cancer Research. First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. J Clin Oncol. 1994 Oct;12(10):2071-7. [https://doi.org/10.1200/JCO.1994.12.10.2071 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7931476 PubMed]
 
−
## '''Update:''' Waeber M, Castiglione-Gertsch M, Dietrich D, Thürlimann B, Goldhirsch A, Brunner KW, Borner MM; Swiss Group for Clinical Cancer Research. Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation. Ann Oncol. 2003 Aug;14(8):1215-21. [https://doi.org/10.1093/annonc/mdg347 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12881382 PubMed]
 
−
# Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I, Schoenfelder J. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. [https://doi.org/10.1200/jco.1995.13.10.2556 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7595707 PubMed]
 
−
# '''SAKK 20/88:''' Thürlimann B, Beretta K, Bacchi M, Castiglione-Gertsch M, Goldhirsch A, Jungi WF, Cavalli F, Senn HJ, Fey M, Löhnert T. First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer: prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88. Ann Oncol. 1996 Jul;7(5):471-9. [https://doi.org/10.1093/oxfordjournals.annonc.a010635 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8839901 PubMed]
 
−
# Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. [https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8943670 PubMed]
 
−
# Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J; Eastern European Study Group. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. [https://doi.org/10.1023/a:1005891506092 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9386869 PubMed]
 
−
# Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'Nordic' phase III study. Br J Cancer. 1997;76(2):270-7. [https://doi.org/10.1038/bjc.1997.375 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9231932 PubMed]
 
−
# '''TARGET<sub>Breast</sub>:''' Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M, von Euler M. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000 Nov 15;18(22):3748-57. Erratum in: J Clin Oncol. 2012 Jan 20;30(3):343. [https://doi.org/10.1200/JCO.2000.18.22.3748 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11078487 PubMed]
 
−
# '''Arimidex Study Group 2000:''' Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M; Arimidex Study Group. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol. 2000 Nov 15;18(22):3758-67. [https://doi.org/10.1200/JCO.2000.18.22.3758 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11078488 PubMed]
 
−
# Milla-Santos A, Milla L, Rallo L, Solano V. Phase III randomized trial of toremifene vs tamoxifen in hormonodependant advanced breast cancer. Breast Cancer Res Treat. 2001 Jan;65(2):119-24. [https://doi.org/10.1023/a:1006440802709 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11261827 PubMed]
 
−
# '''ILBCG:''' Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol. 2001 May 15;19(10):2596-606. Erratum in: J Clin Oncol 2001 Jul 1;19(13):3302. [https://doi.org/10.1200/JCO.2001.19.10.2596 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11352951 PubMed]
 
−
## '''Update:''' Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Chaudri-Ross H, Lang R, Wyld P, Bhatnagar A. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003 Jun 1;21(11):2101-9. [https://doi.org/10.1200/JCO.2003.04.194 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12775735 PubMed]
 
−
# Bajetta E, Procopio G, Ferrari L, Martinetti A, Zilembo N, Catena L, Alú M, Della TS, Alberti D, Buzzoni R. A randomized, multicenter prospective trial assessing long-acting release octreotide pamoate plus tamoxifen as a first line therapy for advanced breast carcinoma. Cancer. 2002 Jan 15;94(2):299-304. [https://doi.org/full/10.1002/cncr.10239 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11900215 PubMed]
 
−
# Buzdar A, Hayes D, El-Khoudary A, Yan S, Lønning P, Lichinitser M, Gopal R, Falkson G, Pritchard K, Lipton A, Wolter K, Lee A, Fly K, Chew R, Alderdice M, Burke K, Eisenber P; Droloxifene 301 Study Group. Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. Breast Cancer Res Treat. 2002 May;73(2):161-75. [https://doi.org/10.1023/a:1015229630260 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12088118 PubMed]
 
−
# Milla-Santos A, Milla L, Portella J, Rallo L, Pons M, Rodes E, Casanovas J, Puig-Gali M. Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer: a prospective, randomized, phase III study. Am J Clin Oncol. 2003 Jun;26(3):317-22. [https://insights.ovid.com/pubmed?pmid=12796608 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12796608 PubMed]
 
−
# Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. [https://doi.org/10.1200/jco.2004.02.112 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15117982 PubMed]
 
−
# '''EORTC 10863:''' Beex L, Rose C, Mouridsen H, Jassem J, Nooij M, Estape J, Paridaens R, Piccart M, Gorlia T, Lardenoije S, Baila L. Continuous versus intermittent tamoxifen versus intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine treatment in advanced breast cancer: an EORTC phase III study (10863). Eur J Cancer. 2006 Dec;42(18):3178-85. Epub 2006 Oct 12. [https://www.ejcancer.com/article/S0959-8049(06)00765-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17045796 PubMed]
 
−
# Deshmane V, Krishnamurthy S, Melemed AS, Peterson P, Buzdar AU. Phase III double-blind trial of arzoxifene compared with tamoxifen for locally advanced or metastatic breast cancer. J Clin Oncol. 2007 Nov 1;25(31):4967-73. [https://doi.org/10.1200/JCO.2006.09.5992 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17971595 PubMed]
 
−
# '''EORTC 10951:''' Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T, Piccart MJ, Bogaerts J, Therasse P; European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol. 2008 Oct 20;26(30):4883-90. Epub 2008 Sep 15. [https://doi.org/10.1200/JCO.2007.14.4659 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652082/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18794551 PubMed] NCT00002777
 
−
==Tamoxifen & Prednisolone {{#subobject:dggabd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:497965|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246832/ Rubens et al. 1988]
 
−
|1981-1986
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19910701)68:1%3C34::AID-CNCR2820680107%3E3.0.CO;2-Q Ingle et al. 1991]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP/OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day
 
−
*[[Prednisolone (Millipred)]] 5 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Rubens RD, Tinson CL, Coleman RE, Knight RK, Tong D, Winter PJ, North WR. Prednisolone improves the response to primary endocrine treatment for advanced breast cancer. Br J Cancer. 1988 Nov;58(5):626-30. [https://doi.org/10.1038/bjc.1988.273 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246832/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3219274 PubMed]
 
−
# Ingle JN, Mailliard JA, Schaid DJ, Krook JE, Gesme DH Jr, Windschitl HE, Pfeifle DM, Etzell PS, Gerstner JG, Long HJ, Foley JF, Loprinzi CL, Dalton RJ; NCCTG. A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer: a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. Cancer. 1991 Jul 1;68(1):34-9. [https://doi.org/10.1002/1097-0142(19910701)68:1%3C34::AID-CNCR2820680107%3E3.0.CO;2-Q link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2049750 PubMed]
 
−
==Toremifene monotherapy {{#subobject:eeba1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:32e0dd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ Pyrhönen et al. 1997]
 
−
|1986-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]; 40 mg/day
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1023/a:1005891506092 Gershanovich et al. 1997]
 
−
| rowspan="2" |1987-1992
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|1. [[#Tamoxifen_monotherapy_4|Tamoxifen]]; 40 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP
 
−
|-
 
−
|2. [[#Toremifene_monotherapy_2|Toremifene]]; 240 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.1995.13.10.2556 Hayes et al. 1995]
 
−
| rowspan="2" |1988-1991
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|1. [[#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|2. [[#Toremifene_monotherapy_2|Toremifene]]; 200 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1023/a:1006440802709 Milla-Santos et al. 2001]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Tamoxifen_monotherapy_4|Tamoxifen]]; 40 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP/OS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Toremifene (Fareston)]] 60 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I, Schoenfelder J. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. [https://doi.org/10.1200/jco.1995.13.10.2556 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7595707 PubMed]
 
−
# Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J; Eastern European Study Group. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. [https://doi.org/10.1023/a:1005891506092 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9386869 PubMed]
 
−
# Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'Nordic' phase III study. Br J Cancer. 1997;76(2):270-7. [https://doi.org/10.1038/bjc.1997.375 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223944/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9231932 PubMed]
 
−
# Milla-Santos A, Milla L, Rallo L, Solano V. Phase III randomized trial of toremifene vs tamoxifen in hormonodependant advanced breast cancer. Breast Cancer Res Treat. 2001 Jan;65(2):119-24. [https://doi.org/10.1023/a:1006440802709 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11261827 PubMed]
 
−
=Metastatic disease, maintenance after first-line therapy=
 
−
==Anastrozole monotherapy {{#subobject:7962bb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bdhgcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2021.05.008 Guarneri et al. 2021 (MAIN-A)]
 
−
|2014-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Everolimus_99|Anastrozole & Everolimus]]<br>2. [[#Everolimus_.26_Exemestane_99|Everolimus & Exemestane]]<br>3. [[#Everolimus_.26_Letrozole_99|Everolimus & Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: this trial accrued less than 50% of the planned patients.''
 
−
====Preceding treatment====
 
−
*At least 6 cycles of "standard" first-line chemotherapy
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#'''MAIN-A:''' Guarneri V, Giorgi CA, Cinieri S, Bengala C, Mariani G, Bisagni G, Frassoldati A, Zamagni C, De Rossi C, Amoroso V, Andreetta C, Ferro A, Zambelli A, Gori S, Garrone O, Dieci MV, Orlando L, Pastina I, Beninato T, Moretti G, Genovesi E, Cinefra M, Vicini R, Magni G, De Salvo GL, Conte P. Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial. Eur J Cancer. 2021 Sep;154:21-29. Epub 2021 Jul 2. [https://doi.org/10.1016/j.ejca.2021.05.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34225066/ PubMed] EudraCT 2013-004153-24
 
−
==Exemestane monotherapy {{#subobject:jib2bb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bdhgcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2021.05.008 Guarneri et al. 2021 (MAIN-A)]
 
−
|2014-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Everolimus_99|Anastrozole & Everolimus]]<br>2. [[#Everolimus_.26_Exemestane_99|Everolimus & Exemestane]]<br>3. [[#Everolimus_.26_Letrozole_99|Everolimus & Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: this trial accrued less than 50% of the planned patients.''
 
−
====Preceding treatment====
 
−
*At least 6 cycles of "standard" first-line chemotherapy
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#'''MAIN-A:''' Guarneri V, Giorgi CA, Cinieri S, Bengala C, Mariani G, Bisagni G, Frassoldati A, Zamagni C, De Rossi C, Amoroso V, Andreetta C, Ferro A, Zambelli A, Gori S, Garrone O, Dieci MV, Orlando L, Pastina I, Beninato T, Moretti G, Genovesi E, Cinefra M, Vicini R, Magni G, De Salvo GL, Conte P. Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial. Eur J Cancer. 2021 Sep;154:21-29. Epub 2021 Jul 2. [https://doi.org/10.1016/j.ejca.2021.05.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34225066/ PubMed] EudraCT 2013-004153-24
 
−
==Letrozole monotherapy {{#subobject:jzl46b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bdhgcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.ejca.2021.05.008 Guarneri et al. 2021 (MAIN-A)]
 
−
|2014-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Everolimus_99|Anastrozole & Everolimus]]<br>2. [[#Everolimus_.26_Exemestane_99|Everolimus & Exemestane]]<br>3. [[#Everolimus_.26_Letrozole_99|Everolimus & Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: this trial accrued less than 50% of the planned patients.''
 
−
====Preceding treatment====
 
−
*At least 6 cycles of "standard" first-line chemotherapy
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#'''MAIN-A:''' Guarneri V, Giorgi CA, Cinieri S, Bengala C, Mariani G, Bisagni G, Frassoldati A, Zamagni C, De Rossi C, Amoroso V, Andreetta C, Ferro A, Zambelli A, Gori S, Garrone O, Dieci MV, Orlando L, Pastina I, Beninato T, Moretti G, Genovesi E, Cinefra M, Vicini R, Magni G, De Salvo GL, Conte P. Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial. Eur J Cancer. 2021 Sep;154:21-29. Epub 2021 Jul 2. [https://doi.org/10.1016/j.ejca.2021.05.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34225066/ PubMed] EudraCT 2013-004153-24
 
−
=Metastatic disease, subsequent lines of therapy=
 
−
==Abemaciclib monotherapy {{#subobject:9cg646|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4r2c78|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5581697/ Dickler et al. 2017 (MONARCH 1)]
 
−
|2014-2015
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
====Targeted therapy====
 
−
*[[Abemaciclib (Verzenio)]] 200 mg PO twice per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MONARCH 1:''' Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224. Epub 2017 May 22. Erratum in: Clin Cancer Res. 2018 Nov 1;24(21):5485. [https://doi.org/10.1158/1078-0432.ccr-17-0754 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5581697/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28533223/ PubMed] NCT02102490
 
−
==Abemaciclib & Fulvestrant {{#subobject:9cf796|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:35ec78|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.73.7585 Sledge et al. 2017 (MONARCH 2)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 46.7 vs 37.3 mo<br>(HR 0.76, 95% CI 0.61-0.95)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2019 update.''
 
−
====Targeted therapy====
 
−
*[[Abemaciclib (Verzenio)]] 150 mg PO twice per day
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONARCH 2:''' Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. [https://doi.org/10.1200/JCO.2017.73.7585 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28580882 PubMed] NCT02107703
 
−
## '''Update:''' Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2019 Sep 29;6(1):116-124. Epub 2019 Sep 29.  [https://jamanetwork.com/journals/jamaoncology/fullarticle/2752266 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777264/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31563959 PubMed]
 
−
==Anastrozole monotherapy {{#subobject:327095|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:62abc2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan = 2|[https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf Jonat et al. 1996]
 
−
|rowspan=2|1993-1994
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Anastrozole_monotherapy_4|Anastrozole]]; 10 mg/day
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|rowspan = 2|[https://doi.org/10.1200/JCO.1996.14.7.2000 Buzdar et al. 1996]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Anastrozole_monotherapy_4|Anastrozole]]; 10 mg/day
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.10.058 Osborne et al. 2002 (Trial 0021)]
 
−
|1997-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]] 250 mg
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.10.057 Howell et al. 2002 (Trial 0020)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]] 250 mg
 
−
| style="background-color:#eeee01" |Seems to have non-inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1016/s0959-8049(03)00630-0 Rose et al. 2003]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (E-swith-ic)
 
−
|[[#Letrozole_monotherapy_5|Letrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1007/s00280-010-1483-x Xu et al. 2010]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]] 250 mg
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Jonat et al. 1996 and Buzdar et al. 1996 is based on the 1998 pooled update.''<br>
 
−
''Note: Buzdar et al. 1996 is an update to Jonat et al. 1996 as well as a primary publication.''
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. [https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8814682 PubMed]
 
−
## '''Pooled update:''' Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://doi.org/10.1200/JCO.1996.14.7.2000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8683230 PubMed]
 
−
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9740079 PubMed]
 
−
# Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://doi.org/10.1200/JCO.1996.14.7.2000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8683230 PubMed]
 
−
## '''Update:''' Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819970215%2979%3A4%3C730%3A%3AAID-CNCR10%3E3.0.CO%3B2-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9024711 PubMed]
 
−
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9740079 PubMed]
 
−
# '''Trial 0021:''' Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, Webster A, Morris C, Elledge R, Buzdar A. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002 Aug 15;20(16):3386-95. [https://doi.org/10.1200/JCO.2002.10.058 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12177098 PubMed] NCT00635713
 
−
## '''Pooled update:''' Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, Buzdar A, Webster A, Morris C. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003 Jul 15;98(2):229-38. [https://doi.org/10.1002/cncr.11468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12872340/ PubMed]
 
−
## '''Pooled update:''' Howell A, Pippen J, Elledge RM, Mauriac L, Vergote I, Jones SE, Come SE, Osborne CK, Robertson JF. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 2005 Jul 15;104(2):236-9. [https://doi.org/full/10.1002/cncr.21163 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15937908 PubMed]
 
−
# '''Trial 0020:''' Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. [https://doi.org/10.1200/jco.2002.10.057 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12177099 PubMed]
 
−
## '''Pooled update:''' Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, Buzdar A, Webster A, Morris C. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003 Jul 15;98(2):229-38. [https://doi.org/10.1002/cncr.11468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12872340/ PubMed]
 
−
## '''Pooled update:''' Howell A, Pippen J, Elledge RM, Mauriac L, Vergote I, Jones SE, Come SE, Osborne CK, Robertson JF. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 2005 Jul 15;104(2):236-9. [https://doi.org/full/10.1002/cncr.21163 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15937908 PubMed]
 
−
# Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R, Johnson S, Caicedo JJ, Gervasio H, Manikhas G, Ben Ayed F, Burdette-Radoux S, Chaudri-Ross HA, Lang R. An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer. 2003 Nov;39(16):2318-27. [https://doi.org/10.1016/s0959-8049(03)00630-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14556923/ PubMed]
 
−
# Xu B, Jiang Z, Shao Z, Wang J, Feng J, Song S, Chen Z, Gu K, Yu S, Zhang Y, Wang C, Zhang F, Yang J. Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial. Cancer Chemother Pharmacol. 2011 Jan;67(1):223-30. Epub 2010 Oct 12. [https://doi.org/10.1007/s00280-010-1483-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/20938664 PubMed]
 
−
==Anastrozole & Fulvestrant {{#subobject:ae2512|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:967cf8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70322-X Johnston et al. 2013 (SoFEA)]
 
−
|2004-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Exemestane_monotherapy_4|Exemestane]]<br> 2. [[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Anastrozole (Arimidex)]] 1 mg PO once per day
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once on day 1, then 250 mg IM once on day 15
 
−
**Cycle 2 onwards: 250 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SoFEA:''' Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, Im YH, Braybrooke JP, Brunt AM, Cheung KL, Jyothirmayi R, Robinson A, Wardley AM, Wheatley D, Howell A, Coombes G, Sergenson N, Sin HJ, Folkerd E, Dowsett M, Bliss JM; SoFEA investigators. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013 Sep;14(10):989-98. Epub 2013 Jul 29. [https://doi.org/10.1016/S1470-2045(13)70322-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23902874 PubMed] NCT00253422; NCT00944918
 
−
==Capecitabine monotherapy {{#subobject:bd9beb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1000 mg/m<sup>2</sup> PO twice per day {{#subobject:4eb6c8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.annonc.2020.12.013 Martin et al. 2020 (PEARL cohort 1)]
 
−
|2014-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 10.6 vs 8 mo<br>(HR 0.90, 95% CI 0.71-1.15)
 
−
|-
 
−
|[https://doi.org/10.1016/j.annonc.2020.12.013 Martin et al. 2020 (PEARL cohort 2)]
 
−
|2016-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Palbociclib_99|Fulvestrant & Palbociclib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 10 vs 7.5 mo<br>(HR 0.88, 95% CI 0.67-1.18)
 
−
|-
 
−
|}
 
−
''Note: this variant was used in patients older than 70 years of age.''
 
−
====Biomarker eligibility criteria====
 
−
*PEARL cohort 2: ESR1 mutations
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1250 mg/m<sup>2</sup> PO twice per day {{#subobject:f3e92c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.annonc.2020.12.013 Martin et al. 2020 (PEARL cohort 1)]
 
−
|2014-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_.26_Palbociclib_99|Exemestane & Palbociclib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 10.6 vs 8 mo<br>(HR 0.90, 95% CI 0.71-1.15)
 
−
|-
 
−
|[https://doi.org/10.1016/j.annonc.2020.12.013 Martin et al. 2020 (PEARL cohort 2)]
 
−
|2016-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Palbociclib_99|Fulvestrant & Palbociclib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 10 vs 7.5 mo<br>(HR 0.88, 95% CI 0.67-1.18)
 
−
|-
 
−
|}
 
−
''Note: this variant was used in patients 70 years of age and younger.''
 
−
====Biomarker eligibility criteria====
 
−
*PEARL cohort 2: ESR1 mutations
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PEARL:''' Martin M, Zielinski C, Ruiz-Borrego M, Carrasco E, Turner N, Ciruelos EM, Muñoz M, Bermejo B, Margeli M, Anton A, Kahan Z, Csöszi T, Casas MI, Murillo L, Morales S, Alba E, Gal-Yam E, Guerrero-Zotano A, Calvo L, de la Haba-Rodriguez J, Ramos M, Alvarez I, Garcia-Palomo A, Huang Bartlett C, Koehler M, Caballero R, Corsaro M, Huang X, Garcia-Sáenz JA, Chacón JI, Swift C, Thallinger C, Gil-Gil M. Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL. Ann Oncol. 2021 Apr;32(4):488-499. Epub 2020 Dec 29. [https://doi.org/10.1016/j.annonc.2020.12.013 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33385521/ PubMed] NCT02028507
 
−
==Capecitabine & Fulvestrant {{#subobject:ae76bj|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:967jc9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.clinical-breast-cancer.com/article/S1526-8209(13)00216-4 Schwartzberg et al. 2013 (ALSSMBC0606)]
 
−
|2007-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] by the following weight-based criteria:
 
−
**Less than 80 kg: 1000 mg PO once every morning and 500 mg PO once every evening
 
−
**80 kg or more: 1000 mg PO twice per day
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once on day 1, then 250 mg IM once on day 15
 
−
**Cycle 2 onwards: 250 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ALSSMBC0606:''' Schwartzberg LS, Wang G, Somer BG, Blakely LJ, Wheeler BM, Walker MS, Stepanski EJ, Houts AC. Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Clin Breast Cancer. 2014 Feb;14(1):13-9. Epub 2013 Sep 27. [https://www.clinical-breast-cancer.com/article/S1526-8209(13)00216-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24268206 PubMed] NCT00534417
 
−
==Everolimus & Exemestane {{#subobject:c6aadc|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fdbaa3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705195/ Baselga et al. 2011 (BOLERO-2)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Exemestane_monotherapy_4|Exemestane]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: 7.8 vs 3.2 mo<br>(HR 0.45, 95% CI 0.38-0.54)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2013 update.''
 
−
====Targeted therapy====
 
−
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''BOLERO-2:''' Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1109653 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705195/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149876 PubMed] NCT00863655
 
−
## '''Update:''' Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. [https://doi.org/10.1007/s12325-013-0060-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898123/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24158787 PubMed]
 
−
## '''Update:''' Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, Noguchi S, Perez A, Rugo HS, Deleu I, Burris HA 3rd, Provencher L, Neven P, Gnant M, Shtivelband M, Wu C, Fan J, Feng W, Taran T, Baselga J. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol. 2014 Dec;25(12):2357-62. Epub 2014 Sep 17. [https://doi.org/10.1093/annonc/mdu456 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6267855/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25231953 PubMed]
 
−
==Everolimus & Tamoxifen {{#subobject:2abaa9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dd6395|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.39.0708 Bachelot et al. 2012 (TAMRAD)]
 
−
|2008-2009
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Tamoxifen_monotherapy_5|Tamoxifen]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: NYR vs 32.9 mo<br>(HR 0.45, 95% CI 0.24-0.81)
 
−
|-
 
−
|}
 
−
====Targeted therapy====
 
−
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010, and 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011. -->
 
−
# '''TAMRAD:''' Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. [https://doi.org/10.1200/JCO.2011.39.0708 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22565002 PubMed] NCT01298713
 
−
==Exemestane monotherapy {{#subobject:a3d882|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:49119f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.7.1399 Kaufmann et al. 2000]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.5822 Chia et al. 2008 (EFECT)]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70322-X Johnston et al. 2013 (SoFEA)]
 
−
|2004-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Anastrozole_.26_Fulvestrant_2|Anastrozole & Fulvestrant]]<br> 2. [[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705195/ Baselga et al. 2011 (BOLERO-2)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Everolimus_.26_Exemestane|Everolimus & Exemestane]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.21.00944 Connolly et al. 2021 (ECOG-ACRIN E2112)]
 
−
|2014-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Entinostat_.26_Exemestane_77|Entinostat & Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(19)30164-0 Jiang et al. 2019 (ACE<sub>brca</sub>)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Exemestane_.26_Tucidinostat|Exemestane & Tucidinostat]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: there is a regimen called ACE; the study is labeled as ACE<sub>brca</sub> to reduce confusion.''
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. [https://doi.org/10.1200/JCO.2000.18.7.1399 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10735887 PubMed]
 
−
##'''Update:''' Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G. Exemestane improves survival in metastatic breast cancer: results of a phase III randomized study. Clin Breast Cancer. 2000 Sep;1 Suppl 1:S15-8. [https://doi.org/10.3816/cbc.2000.s.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11970744/ PubMed]
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium December 14-17, 2006, San Antonio, Texas. -->
 
−
# '''EFECT:''' Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. [https://doi.org/10.1200/jco.2007.13.5822 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18316794 PubMed] NCT00065325
 
−
# '''BOLERO-2:''' Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1109653 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705195/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149876 PubMed] NCT00863655
 
−
## '''Update:''' Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. [https://doi.org/10.1007/s12325-013-0060-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898123/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24158787 PubMed]
 
−
## '''Update:''' Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, Noguchi S, Perez A, Rugo HS, Deleu I, Burris HA 3rd, Provencher L, Neven P, Gnant M, Shtivelband M, Wu C, Fan J, Feng W, Taran T, Baselga J. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol. 2014 Dec;25(12):2357-62. Epub 2014 Sep 17. [https://doi.org/10.1093/annonc/mdu456 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6267855/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25231953 PubMed]
 
−
# '''SoFEA:''' Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, Im YH, Braybrooke JP, Brunt AM, Cheung KL, Jyothirmayi R, Robinson A, Wardley AM, Wheatley D, Howell A, Coombes G, Sergenson N, Sin HJ, Folkerd E, Dowsett M, Bliss JM; SoFEA investigators. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013 Sep;14(10):989-98. Epub 2013 Jul 29. [https://doi.org/10.1016/S1470-2045(13)70322-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23902874 PubMed] NCT00253422; NCT00944918
 
−
# '''ACE:''' Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, Tong Z, Cheng Y, Pan Y, Sun Y, Wang H, Ouyang T, Gu K, Feng J, Wang X, Wang S, Liu T, Gao J, Cristofanilli M, Ning Z, Lu X. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):806-815. Epub 2019 Apr 27. [https://doi.org/10.1016/S1470-2045(19)30164-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31036468 PubMed] NCT02482753
 
−
# '''ECOG-ACRIN E2112:''' Connolly RM, Zhao F, Miller KD, Lee MJ, Piekarz RL, Smith KL, Brown-Glaberman UA, Winn JS, Faller BA, Onitilo AA, Burkard ME, Budd GT, Levine EG, Royce ME, Kaufman PA, Thomas A, Trepel JB, Wolff AC, Sparano JA. E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive Advanced Breast Cancer; A Trial of the ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2021 Oct 1;39(28):3171-3181. Epub 2021 Aug 6. [https://doi.org/10.1200/jco.21.00944 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478386/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34357781/ PubMed] NCT02115282
 
−
==Exemestane & Tucidinostat {{#subobject:a3d443|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48002f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(19)30164-0 Jiang et al. 2019 (ACE<sub>brca</sub>)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Exemestane_monotherapy_4|Exemestane]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 7.4 vs 3.8 mo<br>(HR 0.75, 95% CI 0.58-0.98)
 
−
|-
 
−
|}
 
−
''Note: there is a regimen called ACE; the study is labeled as ACE<sub>brca</sub> to reduce confusion.''
 
−
====Endocrine therapy====
 
−
*[[Exemestane (Aromasin)]] 25 mg PO once per day
 
−
====Targeted therapy====
 
−
*[[Chidamide (Epidaza)]] 30 mg PO once per day on days 1, 4, 8, 11, 15, 18, 22, 25
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ACE:''' Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, Tong Z, Cheng Y, Pan Y, Sun Y, Wang H, Ouyang T, Gu K, Feng J, Wang X, Wang S, Liu T, Gao J, Cristofanilli M, Ning Z, Lu X. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):806-815. Epub 2019 Apr 27. [https://doi.org/10.1016/S1470-2045(19)30164-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31036468 PubMed] NCT02482753
 
−
==Fulvestrant monotherapy {{#subobject:c91702|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 250 mg {{#subobject:2dbfb0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140673695911561 Howell et al. 1995]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 1/2, <20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.10.058 Osborne et al. 2002 (Trial 0021)]
 
−
|1997-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Anastrozole_monotherapy_4|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.10.057 Howell et al. 2002 (Trial 0020)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Anastrozole_monotherapy_4|Anastrozole]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdl341 Perey et al. 2006 (SAKK 21/00)]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.8415 Di Leo et al. 2010 (CONFIRM)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]; 500 mg
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1007/s00280-010-1483-x Xu et al. 2010]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Anastrozole_monotherapy_4|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for CONFIRM is based on the 2013 update.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] 250 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 250 mg, with loading dose {{#subobject:37d8e9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.5822 Chia et al. 2008 (EFECT)]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Exemestane_monotherapy_4|Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70322-X Johnston et al. 2013 (SoFEA)]
 
−
|rowspan=2|2004-2010
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Exemestane_monotherapy_4|Exemestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|2. [[#Anastrozole_.26_Fulvestrant_2|Anastrozole & Fulvestrant]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251959/ Burstein et al. 2014 (CALGB 40302)]
 
−
|2006-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Lapatinib_99|Fulvestrant & Lapatinib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: EFECT states that the 2nd dose of cycle 1 is to be given on day 14, but also notes in the abstract that the first day of the cycle is day 0. Based on other published fulvestrant schedules, we note the second dose as on day 15.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once on day 1, then 250 mg IM once on day 15
 
−
**Cycle 2 onwards: 250 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 500 mg {{#subobject:bd033c|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.28.8415 Di Leo et al. 2010 (CONFIRM)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]; 250 mg
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 26.4 vs 22.3 mo<br>(HR 0.81, 95% CI 0.69-0.96)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549667/ Baselga et al. 2017 (BELLE-2)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Buparlisib_.26_Fulvestrant_77|Buparlisib & Fulvestrant]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>2</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1505270 Turner et al. 2015 (PALOMA-3)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Palbociclib|Fulvestrant & Palbociclib]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>3</sup>
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30688-5 Di Leo et al. 2017 (BELLE-3)]
 
−
|2013-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Buparlisib_.26_Fulvestrant_77|Buparlisib & Fulvestrant]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.73.7585 Sledge et al. 2017 (MONARCH 2)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Abemaciclib_.26_Fulvestrant|Abemaciclib & Fulvestrant]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>4</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.78.9909 Slamon et al. 2018 (MONALEESA-3)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fulvestrant_.26_Ribociclib_2|Fulvestrant & Ribociclib]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>5</sup>
 
−
|-
 
−
|[https://doi.org/10.1038/s41591-021-01562-9 Xu et al. 2021 (DAWNA-1)]
 
−
|2019-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Dalpiciclib_.26_Fulvestrant_77|Dalpiciclib & Fulvestrant]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.22.00338 Bidard et al. 2022 (EMERALD)]
 
−
|2019-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Elacestrant_monotherapy_77|Elacestrant]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for CONFIRM is based on the 2013 update.''<br>
 
−
''<sup>2</sup>Reported efficacy for BELLE-2 is based on the 2018 update.''<br>
 
−
''<sup>3</sup>Reported efficacy for PALOMA-3 is based on the 2022 update.''<br>
 
−
''<sup>4</sup>Reported efficacy for MONARCH 2 is based on the 2019 update.''<br>
 
−
''<sup>5</sup>Reported efficacy for MONALEESA-3 is based on the 2021 update.''<br>
 
−
''Note: while this regimen was inferior in BELLE-2 and BELLE-3, the authors note that "no further studies [of this combination] are being pursued because of the toxicity associated with [the experimental arm]."''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Howell A, DeFriend D, Robertson J, Blamey R, Walton P. Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer. Lancet. 1995 Jan 7;345(8941):29-30. [https://doi.org/10.1016/S0140673695911561 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7799704 PubMed]
 
−
# '''Trial 0021:''' Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, Webster A, Morris C, Elledge R, Buzdar A. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002 Aug 15;20(16):3386-95. [https://doi.org/10.1200/JCO.2002.10.058 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12177098 PubMed] NCT00635713
 
−
## '''Pooled update:''' Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, Buzdar A, Webster A, Morris C. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003 Jul 15;98(2):229-38. [https://doi.org/10.1002/cncr.11468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12872340/ PubMed]
 
−
## '''Pooled update:''' Howell A, Pippen J, Elledge RM, Mauriac L, Vergote I, Jones SE, Come SE, Osborne CK, Robertson JF. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 2005 Jul 15;104(2):236-9. [https://doi.org/full/10.1002/cncr.21163 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15937908 PubMed]
 
−
# '''Trial 0020:''' Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. [https://doi.org/10.1200/jco.2002.10.057 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12177099 PubMed]
 
−
## '''Pooled update:''' Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, Buzdar A, Webster A, Morris C. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003 Jul 15;98(2):229-38. [https://doi.org/10.1002/cncr.11468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12872340/ PubMed]
 
−
## '''Pooled update:''' Howell A, Pippen J, Elledge RM, Mauriac L, Vergote I, Jones SE, Come SE, Osborne CK, Robertson JF. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer. 2005 Jul 15;104(2):236-9. [https://doi.org/full/10.1002/cncr.21163 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15937908 PubMed]
 
−
# '''SAKK 21/00:''' Perey L, Paridaens R, Hawle H, Zaman K, Nolé F, Wildiers H, Fiche M, Dietrich D, Clément P, Köberle D, Goldhirsch A, Thürlimann B. Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol. 2007 Jan;18(1):64-9. Epub 2006 Oct 9. [https://doi.org/10.1093/annonc/mdl341 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17030543 PubMed]
 
−
<!-- Presented in part at the 29th Annual San Antonio Breast Cancer Symposium December 14-17, 2006, San Antonio, Texas. -->
 
−
# '''EFECT:''' Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. [https://doi.org/10.1200/jco.2007.13.5822 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18316794 PubMed] NCT00065325
 
−
# '''CONFIRM:''' Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martín M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4594-600. Epub 2010 Sep 20. Erratum in: J Clin Oncol. 2011 Jun 1;29(16):2293. [https://doi.org/10.1200/JCO.2010.28.8415 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20855825 PubMed] NCT00099437
 
−
## '''Update:''' Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Malorni L, Garnett S, Rukazenkov Y, Martin M. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014 Jan;106(1):djt337. Epub 2013 Dec 7. [https://academic.oup.com/jnci/article/106/1/djt337/2517856 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906991/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24317176 PubMed]
 
−
# Xu B, Jiang Z, Shao Z, Wang J, Feng J, Song S, Chen Z, Gu K, Yu S, Zhang Y, Wang C, Zhang F, Yang J. Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial. Cancer Chemother Pharmacol. 2011 Jan;67(1):223-30. Epub 2010 Oct 12. [https://doi.org/10.1007/s00280-010-1483-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/20938664 PubMed]
 
−
# '''SoFEA:''' Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, Im YH, Braybrooke JP, Brunt AM, Cheung KL, Jyothirmayi R, Robinson A, Wardley AM, Wheatley D, Howell A, Coombes G, Sergenson N, Sin HJ, Folkerd E, Dowsett M, Bliss JM; SoFEA investigators. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013 Sep;14(10):989-98. Epub 2013 Jul 29. [https://doi.org/10.1016/S1470-2045(13)70322-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23902874 PubMed] NCT00253422; NCT00944918
 
−
# '''CALGB 40302:''' Burstein HJ, Cirrincione CT, Barry WT, Chew HK, Tolaney SM, Lake DE, Ma C, Blackwell KL, Winer EP, Hudis CA. Endocrine therapy with or without inhibition of epidermal growth factor receptor and human epidermal growth factor receptor 2: a randomized, double-blind, placebo-controlled phase III trial of fulvestrant with or without lapatinib for postmenopausal women with hormone receptor-positive advanced breast cancer-CALGB 40302 (Alliance). J Clin Oncol. 2014 Dec 10;32(35):3959-66. Epub 2014 Oct 27. [https://doi.org/10.1200/JCO.2014.56.7941 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251959/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25348000 PubMed] NCT00390455
 
−
# '''PALOMA-3:''' Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. [https://doi.org/10.1056/NEJMoa1505270 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26030518 PubMed] NCT01942135
 
−
## '''Update:''' Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. [https://doi.org/10.1016/S1470-2045(15)00613-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26947331 PubMed]
 
−
## '''Subgroup analysis:''' Loibl S, Turner NC, Ro J, Cristofanilli M, Iwata H, Im SA, Masuda N, Loi S, André F, Harbeck N, Verma S, Folkerd E, Puyana Theall K, Hoffman J, Zhang K, Bartlett CH, Dowsett M. Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results. Oncologist. 2017 Sep;22(9):1028-1038. Epub 2017 Jun 26. [http://theoncologist.alphamedpress.org/content/22/9/1028.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599195/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28652278 PubMed]
 
−
## '''Update:''' Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, André F, Puyana Theall K, Huang X, Giorgetti C, Huang Bartlett C, Cristofanilli M. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018 Nov 15;379(20):1926-1936. Epub 2018 Oct 20. [https://doi.org/10.1056/NEJMoa1810527 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30345905 PubMed]
 
−
## '''Update:''' Cristofanilli M, Rugo HS, Im SA, Slamon DJ, Harbeck N, Bondarenko I, Masuda N, Colleoni M, DeMichele A, Loi S, Iwata H, O'Leary B, André F, Loibl S, Bananis E, Liu Y, Huang X, Kim S, Lechuga Frean MJ, Turner NC. Overall Survival with Palbociclib and Fulvestrant in Women with HR+/HER2- ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study. Clin Cancer Res. 2022 Aug 15;28(16):3433-3442. [https://doi.org/10.1158/1078-0432.ccr-22-0305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35552673/ PubMed]
 
−
# '''BELLE-2:''' Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. Epub 2017 May 30. [https://doi.org/10.1016/S1470-2045(17)30376-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549667/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28576675 PubMed] NCT01610284
 
−
## '''Update:''' Campone M, Im SA, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Cortés J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Le Mouhaër S, Sankaran B, Bourdeau L, El-Hashimy M, Sellami D, Baselga J. Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: overall survival results from BELLE-2. Eur J Cancer. 2018 Nov;103:147-154. Epub 2018 Sep 18. [https://www.ejcancer.com/article/S0959-8049(18)31112-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30241001 PubMed]
 
−
# '''MONARCH-2:''' Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. [https://doi.org/10.1200/JCO.2017.73.7585 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28580882 PubMed] NCT02107703
 
−
## '''Update:''' Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2019 Sep 29;6(1):116-124. Epub 2019 Sep 29.  [https://jamanetwork.com/journals/jamaoncology/fullarticle/2752266 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777264/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31563959 PubMed]
 
−
# '''BELLE-3:''' Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csőszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):87-100. Epub 2017 Dec 7. [https://doi.org/10.1016/S1470-2045(17)30688-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29223745 PubMed] NCT01633060
 
−
# '''MONALEESA-3:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. Epub 2018 Jun 3. [https://doi.org/10.1200/JCO.2018.78.9909 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29860922 PubMed] NCT02422615
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. Epub 2019 Dec 11. [https://doi.org/10.1056/NEJMoa1911149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31826360 PubMed]
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. Epub 2021 Jun 5. Erratum in: Ann Oncol. 2021 Oct;32(10):1307. [https://doi.org/10.1016/j.annonc.2021.05.353 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34102253/ PubMed]
 
−
#'''DAWNA-1:''' Xu B, Zhang Q, Zhang P, Hu X, Li W, Tong Z, Sun T, Teng Y, Wu X, Ouyang Q, Yan X, Cheng J, Liu Q, Feng J, Wang X, Yin Y, Shi Y, Pan Y, Wang Y, Xie W, Yan M, Liu Y, Yan P, Wu F, Zhu X, Zou J; DAWNA-1 Study Consortium. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021 Nov;27(11):1904-1909. Epub 2021 Nov 4. [https://doi.org/10.1038/s41591-021-01562-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34737452/ PubMed] NCT03927456
 
−
#'''EMERALD:''' Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, García Sáenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortés J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256. Epub 2022 May 18. [https://doi.org/10.1200/jco.22.00338 link to original article] '''does not contain dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35584336/ PubMed] NCT03778931
 
−
==Fulvestrant & Palbociclib {{#subobject:a59b43|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f3a761|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1505270 Turner et al. 2015 (PALOMA-3)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 34.8 vs 28 mo<br>(HR 0.81, 95% CI 0.65-0.99)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
====Targeted therapy====
 
−
*[[Palbociclib (Ibrance)]] 125 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''PALOMA-3:''' Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. [https://doi.org/10.1056/NEJMoa1505270 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26030518 PubMed] NCT01942135
 
−
## '''Update:''' Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. [https://doi.org/10.1016/S1470-2045(15)00613-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26947331 PubMed]
 
−
## '''Subgroup analysis:''' Loibl S, Turner NC, Ro J, Cristofanilli M, Iwata H, Im SA, Masuda N, Loi S, André F, Harbeck N, Verma S, Folkerd E, Puyana Theall K, Hoffman J, Zhang K, Bartlett CH, Dowsett M. Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results. Oncologist. 2017 Sep;22(9):1028-1038. Epub 2017 Jun 26. [http://theoncologist.alphamedpress.org/content/22/9/1028.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599195/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28652278 PubMed]
 
−
## '''Update:''' Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, André F, Puyana Theall K, Huang X, Giorgetti C, Huang Bartlett C, Cristofanilli M. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018 Nov 15;379(20):1926-1936. Epub 2018 Oct 20. [https://doi.org/10.1056/NEJMoa1810527 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30345905 PubMed]
 
−
## '''Update:''' Cristofanilli M, Rugo HS, Im SA, Slamon DJ, Harbeck N, Bondarenko I, Masuda N, Colleoni M, DeMichele A, Loi S, Iwata H, O'Leary B, André F, Loibl S, Bananis E, Liu Y, Huang X, Kim S, Lechuga Frean MJ, Turner NC. Overall Survival with Palbociclib and Fulvestrant in Women with HR+/HER2- ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study. Clin Cancer Res. 2022 Aug 15;28(16):3433-3442. [https://doi.org/10.1158/1078-0432.ccr-22-0305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35552673/ PubMed]
 
−
==Fulvestrant & Ribociclib {{#subobject:0c6a05|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ade594|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.78.9909 Slamon et al. 2018 (MONALEESA-3)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Fulvestrant_monotherapy_2|Fulvestrant]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 53.7 vs 41.5 mo<br>(HR 0.73, 95% CI 0.59-0.90)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''
 
−
====Endocrine therapy====
 
−
*[[Fulvestrant (Faslodex)]] as follows:
 
−
**Cycle 1: 500 mg IM once per day on days 1 & 15
 
−
**Cycle 2 onwards: 500 mg IM once on day 1
 
−
====Targeted therapy====
 
−
*[[Ribociclib (Kisqali)]] 600 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MONALEESA-3:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. Epub 2018 Jun 3. [https://doi.org/10.1200/JCO.2018.78.9909 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29860922 PubMed] NCT02422615
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. Epub 2019 Dec 11. [https://doi.org/10.1056/NEJMoa1911149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31826360 PubMed]
 
−
## '''Update:''' Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. Epub 2021 Jun 5. Erratum in: Ann Oncol. 2021 Oct;32(10):1307. [https://doi.org/10.1016/j.annonc.2021.05.353 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34102253/ PubMed]
 
−
==Letrozole monotherapy {{#subobject:230132|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:458647|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998 (AR/BC2)]
 
−
|rowspan=2|1993-1994
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
 
−
|1. [[#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTTF
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1023/a:1008226721932 Gershanovich et al. 1998 (AR/BC3)]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851"|Randomized (E-RT-switch-ic)
 
−
|1. [[#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001]
 
−
|rowspan=2|NR
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|1. [[#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|2. [[Breast_cancer_-_historical#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/s0959-8049(03)00630-0 Rose et al. 2003]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (E-swith-ic)
 
−
|[[#Anastrozole_monotherapy_5|Anastrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
====Endocrine therapy====
 
−
*[[Letrozole (Femara)]] 2.5 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''AR/BC2:''' Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. [https://doi.org/10.1200/JCO.1998.16.2.453 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9469328 PubMed]
 
−
# '''AR/BC3:''' Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P, O'Higgins N, Romieu G, Friederich P, Lassus M; Letrozole International Trial Group. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998 Jun;9(6):639-45. [https://doi.org/10.1023/a:1008226721932 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9681078 PubMed]
 
−
# Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. [https://doi.org/10.1200/JCO.2001.19.14.3357 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11454883 PubMed]
 
−
# Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R, Johnson S, Caicedo JJ, Gervasio H, Manikhas G, Ben Ayed F, Burdette-Radoux S, Chaudri-Ross HA, Lang R. An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer. 2003 Nov;39(16):2318-27. [https://doi.org/10.1016/s0959-8049(03)00630-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14556923/ PubMed]
 
−
==Tamoxifen monotherapy {{#subobject:8bc09f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a1e733|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/365603 Legha et al. 1979]
 
−
|1977
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.7326/0003-4819-98-2-139 Tormey et al. 1983]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Fluoxymesterone_.26_Tamoxifen_77|Fluoxymesterone & Tamoxifen]]
 
−
| style="background-color:#d73027" |Inferior TTTF
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.39.0708 Bachelot et al. 2012 (TAMRAD)]
 
−
|2008-2009
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Everolimus_.26_Tamoxifen|Everolimus & Tamoxifen]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: Tormey et al. 1983 specified a wide range of tamoxifen dosing; see paper for details.''
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Legha SS, Buzdar AU, Hortobagyi GN, Wiseman C, Benjamin RS, Blumenschein GR. Tamoxifen: use in treatment of metastatic breast cancer refractory to combination chemotherapy. JAMA. 1979 Jul 6;242(1):49-52. [https://jamanetwork.com/journals/jama/article-abstract/365603 link to original article] [https://pubmed.ncbi.nlm.nih.gov/448865 PubMed]
 
−
# Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med. 1983 Feb;98(2):139-44. [https://doi.org/10.7326/0003-4819-98-2-139 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6824247 PubMed]
 
−
<!-- Presented in part at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010, and 2011 European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011. -->
 
−
# '''TAMRAD:''' Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E; GINECO. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. [https://doi.org/10.1200/JCO.2011.39.0708 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22565002 PubMed] NCT01298713
 
−
[[Category:Breast cancer regimens]]
 
−
[[Category:Biomarker-specific pages]]
 
−
[[Category:Malignant breast neoplasm]]
 

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