Latest revision as of 12:11, 23 June 2024

Back to Top

Section editor
	TBA

Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the main breast cancer page, ER+ breast cancer page, and HER2+ breast cancer page for other regimens.

19 regimens on this page 21 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO/CAP

2023: Wolff et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO–College of American Pathologists Guideline Update PubMed
2020: Allison et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update PubMed
- 2010: Hammond et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer PubMed

NCCN

NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer.

Neoadjuvant chemotherapy

Trastuzumab emtansine monotherapy

T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-switch-ic)	1. T-DM1 & ET	Not reported
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-switch-ic)	2. Trastuzumab & ET	Superior pCR rate (primary endpoint)

Antibody-drug conjugate therapy

Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

21-day cycle for 4 cycles

Subsequent treatment

Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC-TH, unless the patient had pCR in which case adjuvant therapy was optional

References

WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452

T-DM1 & ET

T-DM1 & ET: Trastuzumab-DM1 (Trastuzumab emtansine) & Endocrine Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-esc)	1. T-DM1	Not reported
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-esc)	2. Trastuzumab & ET	Superior pCR rate (primary endpoint)

Antibody-drug conjugate therapy

Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

Endocrine therapy

One of the following:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended

21-day cycle for 4 cycles

Subsequent treatment

Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC-TH, unless the patient had pCR in which case adjuvant therapy was optional

References

WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452

Trastuzumab & ET

Trastuzumab & ET: Trastuzumab & Endocrine Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (C)	1. T-DM1 2. T-DM1 & ET	Inferior pCR rate

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1

Endocrine therapy

Endocrine therapy by the following criteria:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
  - GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended

21-day cycle for 4 cycles

Subsequent treatment

Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC-TH, unless the patient had pCR in which case adjuvant therapy was optional

References

WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452

Adjuvant therapy

Anastrozole monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (eMonarcHER)	2021-ongoing	Phase 3 (C)	ET & Abemaciclib	In progress

Preceding treatment

Adjuvant HER2-targeted therapy

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

Up to 10-year course

References

eMonarcHER: NCT04752332

Metastatic disease, first-line therapy

Anastrozole monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (C)	Anastrozole & Trastuzumab	Inferior PFS

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 28

28-day cycles

References

TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00022672

Anastrozole & Trastuzumab

Regimen variant #1, weekly trastuzumab

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (E-esc)	Anastrozole	Superior PFS (primary endpoint) Median PFS: 4.8 vs 2.4 mo (HR 0.63, 95% CI 0.47-0.84)

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 28

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #2, q3wk trastuzumab

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH	Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 21

21-day cycles

References

TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00022672
ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182

Anastrozole, Lapatinib, Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab	Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day on days 1 to 21
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 21

21-day cycles

References

ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211

Capecitabine & Trastuzumab (XH)

XH: Xeloda (Capecitabine) & Herceptin (Trastuzumab)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (C)	1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab	Non-inferior PFS (primary endpoint)

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182

Docetaxel & Trastuzumab (TH)

TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (C)	1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab	Non-inferior PFS (primary endpoint)

Chemotherapy

Docetaxel (Taxotere) 75 to 100 mg/m² IV once on day 1

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182

Exemestane & Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH	Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Exemestane (Aromasin) 1 mg PO once per day on days 1 to 21

21-day cycles

References

ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182

Exemestane, Lapatinib, Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab	Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day on days 1 to 21
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Exemestane (Aromasin) 25 mg PO once per day on days 1 to 21

21-day cycles

References

ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211

Lapatinib & Letrozole

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (E-RT-esc)	Letrozole	Seems to have superior PFS (primary endpoint) Median PFS: 8.2 vs 3 mo (HR 0.71, 95% CI 0.53-0.96)

Targeted therapy

Lapatinib (Tykerb) 1500 mg PO once per day

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day

Continued indefinitely

References

EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00073528

Lapatinib, Letrozole, Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab	Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day on days 1 to 21
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day on days 1 to 21

21-day cycles

References

ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211

Letrozole monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (C)	Lapatinib & Letrozole	Seems to have inferior PFS

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day on days 1 to 28

28-day cycles

References

EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00073528

Letrozole & Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH	Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day on days 1 to 21

21-day cycles

References

ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182

Paclitaxel & Trastuzumab (TH)

TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (C)	1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab	Non-inferior PFS (primary endpoint)

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1 & 8

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182

Tamoxifen & Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH	Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: Hua et al. 2022 does not contain dosing instructions for tamoxifen; this is a commonly used dosage.

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 21

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182

Toremifene & Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH	Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: Hua et al. 2022 does not contain dosing instructions for toremifene; this is a commonly used dosage.

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

Toremifene (Fareston) 60 mg PO once per day on days 1 to 21

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182

Vinorelbine & Trastuzumab (VH)

VH: Vinorelbine & Herceptin (Trastuzumab)

Regimen variant #1, IV

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (C)	1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab	Non-inferior PFS (primary endpoint)

Chemotherapy

Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

Regimen variant #2, PO

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (C)	1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab	Non-inferior PFS (primary endpoint)

Chemotherapy

Vinorelbine (Navelbine) 60 to 80 mg/m² PO once per day on days 1 & 8

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|breast}}
+{{#lst:Editorial board transclusions|breast}}
 <big>'''Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the [[breast cancer|main breast cancer page]], [[Breast cancer, ER-positive|ER+ breast cancer page]], and [[Breast cancer, HER2-positive|HER2+ breast cancer page]] for other regimens.'''</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
@@ Line 11: / Line 11: @@
 |}
 {{TOC limit|limit=3}}
+=Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
+==ASCO/CAP==
+*'''2023:''' Wolff et al. [https://doi.org/10.1200/jco.22.02864 Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO–College of American Pathologists Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/37284804/ PubMed]
+**'''2014:''' Wolff et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4086638/ Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/24099077/ PubMed]
+**'''2013:''' Wolff et al. [https://doi.org/10.1200/jco.2013.50.9984 Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/24101045/ PubMed]
+**'''2007:''' Wolff et al. [https://doi.org/10.5858/2007-131-18-asocco American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer] [https://pubmed.ncbi.nlm.nih.gov/19548375/ PubMed]
+*'''2020:''' Allison et al. [https://doi.org/10.1200/jco.19.02309 Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/31928404/ PubMed]
+**'''2010:''' Hammond et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2881855/ American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer] [https://pubmed.ncbi.nlm.nih.gov/20404251/ PubMed]
+==NCCN==
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419 NCCN Guidelines - Breast Cancer].''
 =Neoadjuvant chemotherapy=
 ==Trastuzumab emtansine monotherapy {{#subobject:ef98f0|Regimen=1}}==
 T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:91b517|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 31: / Line 43: @@
 |-
 |2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]]
-|style="background-color:#1a9850"|Superior pCR rate
+|style="background-color:#1a9850"|Superior pCR rate (primary endpoint)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1
 '''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional
+</div></div>
 ===References===
-# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
+# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452]
 ==T-DM1 & ET {{#subobject:207386|Regimen=1}}==
 T-DM1 & ET: '''<u>T</u>'''rastuzumab-DM1 (Trastuzumab emtansine) & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b28ce1|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 62: / Line 75: @@
 |-
 |2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]]
-|style="background-color:#1a9850"|Superior pCR rate
+|style="background-color:#1a9850"|Superior pCR rate (primary endpoint)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1
 ====Endocrine therapy====
 *One of the following:
@@ Line 73: / Line 86: @@
 **[[:Category:GnRH_agonists|GnRH analogs]] were also allowed
 **Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended
 '''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional
+</div></div>
 ===References===
-# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
+# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452]
 ==Trastuzumab & ET {{#subobject:b9d62c|Regimen=1}}==
 Trastuzumab & ET: Trastuzumab & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:d0233|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 95: / Line 108: @@
 |2012-2015
 |style="background-color:#1a9851"|Randomized Phase 2 (C)
-|1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]]<br> 2. [[#T-DM1_.26_ET|T-DM1 & ET]]
+|1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]]<br>2. [[#T-DM1_.26_ET|T-DM1 & ET]]
 |style="background-color:#d73027"|Inferior pCR rate
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Trastuzumab (Herceptin)]] as follows:
@@ Line 108: / Line 122: @@
 ***[[:Category:GnRH_agonists|GnRH analogs]] were also allowed
 **Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended
 '''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional
+</div></div>
 ===References===
-# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
+# '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452]
 =Adjuvant therapy=
 ==Anastrozole monotherapy {{#subobject:79h35|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:gav33c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|Awaiting publication (eMonarcHER)
+|[https://www.clinicaltrials.gov/study/NCT04752332 Awaiting publication (eMonarcHER)]
 |2021-ongoing
 |style="background-color:#1a9851"|Phase 3 (C)
-|[[#ET_.26_Abemaciclib_88|ET & Abemaciclib]]
+|[[#ET_.26_Abemaciclib_666|ET & Abemaciclib]]
 | style="background-color:#d3d3d3" |In progress
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*HER2-targeted therapy
+*Adjuvant [[Regimen_classes#Anti-HER2-based_regimen|HER2-targeted therapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Anastrozole (Arimidex)]] 1 mg PO once per day
+'''Up to 10-year course'''
+</div></div>
-'''Continued for up to 10 years'''
 ===References===
-#'''eMonarcHER:''' NCT04752332
+#'''eMonarcHER:''' [https://clinicaltrials.gov/study/NCT04752332 NCT04752332]
 =Metastatic disease, first-line therapy=
 ==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%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 161: / Line 179: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 28
 '''28-day cycles'''
+</div></div>
 ===References===
-# '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670 PubMed] NCT00022672
+# '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670/ PubMed] [https://clinicaltrials.gov/study/NCT00022672 NCT00022672]
 ==Anastrozole & Trastuzumab {{#subobject:8077ad|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, weekly trastuzumab {{#subobject:e6f8f0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 182: / Line 200: @@
 |style="background-color:#1a9851"|Phase 3 (E-esc)
 |[[#Anastrozole_monotherapy_2|Anastrozole]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.8 vs 2.4 mo<br>(HR 0.63, 95% CI 0.47-0.84)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 4.8 vs 2.4 mo<br>(HR 0.63, 95% CI 0.47-0.84)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 28
 ====Targeted therapy====
 *[[Trastuzumab (Herceptin)]] as follows:
 **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
 **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22
 '''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, q3wk trastuzumab {{#subobject:ugibx4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 205: / Line 224: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br> 3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br> 1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 |-
-|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
+|2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
 | style="background-color:#d73027" |Inferior PFS
 |-
-|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
 |2013-2019
 |style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+|1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
-| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
 |-
 |}
 ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Trastuzumab (Herceptin)]] as follows:
@@ Line 224: / Line 244: @@
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 21
 '''21-day cycles'''
+</div></div>
 ===References===
-# '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670 PubMed] NCT00022672
+# '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670/ PubMed] [https://clinicaltrials.gov/study/NCT00022672 NCT00022672]
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
-# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
 ==Anastrozole, Lapatinib, Trastuzumab {{#subobject:gg0dbc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:ug8a84|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 247: / Line 265: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#d3d3d3" |Not reported
 |-
-|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
+|2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
 |-
 |}
 ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21
 *[[Trastuzumab (Herceptin)]] as follows:
 **Cycle 1: 8 mg/kg IV once on day 1
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
+==Capecitabine & Trastuzumab (XH) {{#subobject:677608|Regimen=1}}==
+XH: '''<u>X</u>'''eloda (Capecitabine) & '''<u>H</u>'''erceptin (Trastuzumab)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:a1b284|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
+==Docetaxel & Trastuzumab (TH) {{#subobject:a0af2c|Regimen=1}}==
+TH: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:a1bzcn|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 to 100 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
 ==Exemestane & Trastuzumab {{#subobject:ugjxbc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1yga84|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 282: / Line 359: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 |-
-|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
+|2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
 | style="background-color:#d73027" |Inferior PFS
 |-
-|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
 |2013-2019
 |style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+|1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
-| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
 |-
 |}
 ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Trastuzumab (Herceptin)]] as follows:
@@ Line 301: / Line 379: @@
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Exemestane (Aromasin)]] 1 mg PO once per day
+*[[Exemestane (Aromasin)]] 1 mg PO once per day on days 1 to 21
 '''21-day cycles'''
+</div></div>
 ===References===
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
-# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
 ==Exemestane, Lapatinib, Trastuzumab {{#subobject:hh0dbc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:258gja|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 322: / Line 400: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#d3d3d3" |Not reported
 |-
-|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
+|2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
 |-
 |}
 ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21
 *[[Trastuzumab (Herceptin)]] as follows:
 **Cycle 1: 8 mg/kg IV once on day 1
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Exemestane (Aromasin)]] 25 mg PO once per day
+*[[Exemestane (Aromasin)]] 25 mg PO once per day on days 1 to 21
 '''21-day cycles'''
+</div></div>
 ===References===
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
 ==Lapatinib & Letrozole {{#subobject:5fba83|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:879969|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 358: / Line 435: @@
 |style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 |[[#Letrozole_monotherapy_3|Letrozole]]
-| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 8.2 vs 3 mo<br>(HR 0.71, 95% CI 0.53-0.96)
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 8.2 vs 3 mo<br>(HR 0.71, 95% CI 0.53-0.96)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Lapatinib (Tykerb)]] 1500 mg PO once per day
 ====Endocrine therapy====
 *[[Letrozole (Femara)]] 2.5 mg PO once per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
-# '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658 PubMed] NCT00073528
+# '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658/ PubMed] [https://clinicaltrials.gov/study/NCT00073528 NCT00073528]
 ==Lapatinib, Letrozole, Trastuzumab {{#subobject:ee0dbc|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:251384|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 384: / Line 460: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#d3d3d3" |Not reported
 |-
-|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
+|2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
 |-
 |}
 ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21
 *[[Trastuzumab (Herceptin)]] as follows:
 **Cycle 1: 8 mg/kg IV once on day 1
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Letrozole (Femara)]] 2.5 mg PO once per day
+*[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 21
 '''21-day cycles'''
+</div></div>
 ===References===
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
 ==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%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 423: / Line 498: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Letrozole (Femara)]] 2.5 mg PO once per day
+*[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 28
 '''28-day cycles'''
+</div></div>
 ===References===
-# '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658 PubMed] NCT00073528
+# '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658/ PubMed] [https://clinicaltrials.gov/study/NCT00073528 NCT00073528]
 ==Letrozole & Trastuzumab {{#subobject:8ugz41|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6cq284|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 443: / Line 518: @@
 |rowspan=2|2011-2016
 |rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+|1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
 | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 |-
-|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
+|2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
 | style="background-color:#d73027" |Inferior PFS
 |-
-|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
 |2013-2019
 |style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+|1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
-| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
 |-
 |}
 ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Trastuzumab (Herceptin)]] as follows:
@@ Line 462: / Line 538: @@
 **Cycle 2 onwards: 6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Letrozole (Femara)]] 2.5 mg PO once per day
+*[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] -->
+# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211]
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
+==Paclitaxel & Trastuzumab (TH) {{#subobject:aa22dd|Regimen=1}}==
+TH: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:a1ga84|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
+==Tamoxifen & Trastuzumab {{#subobject:8jnc41|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:1tex84|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
+|-
+|}
+''Note: Hua et al. 2022 does not contain dosing instructions for tamoxifen; this is a commonly used dosage.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+====Endocrine therapy====
+*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day on days 1 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
+==Toremifene & Trastuzumab {{#subobject:torc41|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:1tecx5|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
+|-
+|}
+''Note: Hua et al. 2022 does not contain dosing instructions for toremifene; this is a commonly used dosage.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+====Endocrine therapy====
+*[[Toremifene (Fareston)]] 60 mg PO once per day on days 1 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
+==Vinorelbine & Trastuzumab (VH) {{#subobject:59edc1|Regimen=1}}==
+VH: '''<u>V</u>'''inorelbine & '''<u>H</u>'''erceptin (Trastuzumab)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, IV {{#subobject:hgu44n|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, PO {{#subobject:hur42n|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates 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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)]
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (C)
+|1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]]
+| style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vinorelbine (Navelbine)]] 60 to 80 mg/m<sup>2</sup> PO once per day on days 1 & 8
+====Targeted therapy====
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
 '''21-day cycles'''
+</div></div>
 ===References===
-<!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182]
-# '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
-# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
 [[Category:Breast cancer regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Malignant breast neoplasm]]

Difference between revisions of "Breast cancer, ER and HER2 co-expressing"

Latest revision as of 12:11, 23 June 2024

Guidelines

ASCO/CAP

NCCN

Neoadjuvant chemotherapy

Trastuzumab emtansine monotherapy

Regimen

Antibody-drug conjugate therapy

Subsequent treatment

References

T-DM1 & ET

Regimen

Antibody-drug conjugate therapy

Endocrine therapy

Subsequent treatment

References

Trastuzumab & ET

Regimen

Targeted therapy

Endocrine therapy

Subsequent treatment

References

Adjuvant therapy

Anastrozole monotherapy

Regimen

Preceding treatment

Endocrine therapy

References

Metastatic disease, first-line therapy

Anastrozole monotherapy

Regimen

Endocrine therapy

References

Anastrozole & Trastuzumab

Regimen variant #1, weekly trastuzumab

Endocrine therapy

Targeted therapy

Regimen variant #2, q3wk trastuzumab

Targeted therapy

Endocrine therapy

References

Anastrozole, Lapatinib, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Capecitabine & Trastuzumab (XH)

Regimen

Chemotherapy

Targeted therapy

References

Docetaxel & Trastuzumab (TH)

Regimen

Chemotherapy

Targeted therapy

References

Exemestane & Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Exemestane, Lapatinib, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Lapatinib & Letrozole

Regimen

Targeted therapy

Endocrine therapy

References

Lapatinib, Letrozole, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Letrozole monotherapy

Regimen

Endocrine therapy