Breast cancer, triple negative

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Hermina Fernandes, MD
Bismarck, ND

Note: this page has regimens which are specific to breast cancer that is triple negative. Please see the breast cancer page for other chemotherapy regimens.

13 regimens on this page
13 variants on this page

Contents


Guidelines

ASCO

Neoadjuvant chemotherapy

AC

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AC: Adriamycin (Doxorubicin) & Cyclophosphamide

Regimen

Study Evidence
Rugo et al. 2016 (I-SPY 2) Non-randomized portion of RCT

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

  • T x 12 wk versus Paclitaxel & VC x 12 wk

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery

References

  1. I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed

Carboplatin & Docetaxel

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CbD: Carboplatin & Docetaxel

Regimen

Study Evidence ORR
Sharma et al. 2016 Phase II 56-59% pCR rate

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

  • Surgery

References

  1. Sharma P, López-Tarruella S, García-Saenz JA, Ward C, Connor CS, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Del Monte-Millán M, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortes J, Fuentes Rivera H, Bretel Morales D, Márquez-Rodas I, Perou CM, Wagner JL, Mammen JM, McGinness MK, Klemp JR, Amin AL, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of neoadjuvant carboplatin plus docetaxel in triple-negative breast cancer: Combined analysis of two cohorts. Clin Cancer Res. 2017 Feb 1;23(3):649-657. Epub 2016 Jun 14. link to original article contains protocol link to PMC article PubMed

Carboplatin & Paclitaxel

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Regimen

Study Evidence Comparator Efficacy
Loibl et al. 2018 (BrighTNess) Phase III (E) Carboplatin, Paclitaxel, Veliparib Seems not superior
Paclitaxel Not reported in abstract

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • AC x 4 or ddAC x 4, then surgery

References

  1. BrighTNess: Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. Epub 2018 Feb 28. link to original article contain protocol PubMed

Cisplatin monotherapy

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Regimen

Study Evidence Efficacy
Silver et al. 2010 Phase II 50% good pathologic response

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery

References

  1. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1145-53. Epub 2010 Jan 25. link to original article contains verified protocol link to PMC article PubMed

ddAC

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ddAC: dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide

Regimen

Study Evidence
Rugo et al. 2016 (I-SPY 2) Non-randomized portion of RCT

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

  • T x 12 wk versus Paclitaxel & VC x 12 wk

Chemotherapy

Supportive medications

14-day cycle for 4 cycles

Subsequent treatment

  • Surgery

References

  1. CALGB 40603: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. Epub 2014 Aug 4. link to original article link to PMC article PubMed
  2. I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed

Docetaxel & Bevacizumab

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Regimen

Study Evidence Comparator Efficacy
von Minckwitz et al. 2012 (GeparQuinto) Phase III See link See link

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery

References

  1. von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed

EC & Bevacizumab

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EC & Bevacizumab: Epirubicin, Cyclophosphamide, Bevacizumab

Regimen

Study Evidence Comparator Efficacy
von Minckwitz et al. 2012 (GeparQuinto) Phase III See link See link

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

References

  1. von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed

Paclitaxel monotherapy

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T: Taxol (Paclitaxel)

Regimen

Study Evidence Comparator Efficacy
Rugo et al. 2016 (I-SPY 2) Adaptively Randomized Phase II Paclitaxel & VC Seems to have inferior pCR rate
Loibl et al. 2018 (BrighTNess) Phase III (C) Carboplatin & Paclitaxel Not reported in abstract
Carboplatin, Paclitaxel, Veliparib Inferior pCR rate

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

12-week course

Subsequent treatment

  • AC x 4 or ddAC x 4, then surgery

References

  1. CALGB 40603: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. Epub 2014 Aug 4. link to original article link to PMC article PubMed
  2. I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed
  3. BrighTNess: Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. Epub 2018 Feb 28. link to original article contain protocol PubMed

Adjuvant chemotherapy

Bevacizumab-containing therapy

This was an important negative trial, so is included here for reference purposes, only.

References

  1. Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X, Steger GG, Suter TM, Toi M, Parmar M, Laeufle R, Im YH, Romieu G, Harvey V, Lipatov O, Pienkowski T, Cottu P, Chan A, Im SA, Hall PS, Bubuteishvili-Pacaud L, Henschel V, Deurloo RJ, Pallaud C, Bell R. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013 Sep;14(10):933-42. Epub 2013 Aug 7. link to original article PubMed

Metastatic disease, first-line therapy

Carboplatin & Gemcitabine

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GC: Gemcitabine & Carboplatin

Regimen

Study Evidence Comparator Efficacy
O'Shaughnessy et al. 2014 Phase III (C) GC & Iniparib Might have inferior PFS

Chemotherapy

21-day cycles

References

  1. O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3840-7. Epub 2014 Oct 27. link to original article contains protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study Evidence Comparator Efficacy
Hu et al. 2015 (CBCSG006) Phase III Gemcitabine & Paclitaxel Superior PFS

Chemotherapy

21-day cycle for up to 8 cycles

References

  1. CBCSG006: Hu XC, Zhang J, Xu BH, Cai L, Ragaz J, Wang ZH, Wang BY, Teng YE, Tong ZS, Pan YY, Yin YM, Wu CP, Jiang ZF, Wang XJ, Lou GY, Liu DG, Feng JF, Luo JF, Sun K, Gu YJ, Wu J, Shao ZM. Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):436-46. Epub 2015 Mar 18. link to original article contains protocol PubMed

Paclitaxel monotherapy

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Regimen, 80 mg/m2 3 weeks on, 1 week off

Study Evidence Comparator Efficacy
Kim et al. 2017 (LOTUS) Randomized Phase II (C) Ipatasertib & Paclitaxel Seems to have inferior PFS

Chemotherapy

28-day cycles

References

  1. LOTUS: Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1360-1372. Epub 2017 Aug 8. link to original article PubMed

Metastatic disease, subsequent lines of therapy

Capecitabine & Ixabepilone

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Regimen

Study Evidence Comparator Efficacy
Thomas et al. 2007 Phase III (E) Capecitabine Superior PFS

Note: 25% of the patients in this trial had TNBC.

Chemotherapy

21-day cycles

References

  1. Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed

Carboplatin & Gemcitabine

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GC: Gemcitabine & Carboplatin

Regimen

Study Evidence Comparator Efficacy
O'Shaughnessy et al. 2014 Phase III (C) GC & Iniparib Might have inferior PFS

Chemotherapy

21-day cycles

References

  1. O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3840-7. Epub 2014 Oct 27. link to original article contains protocol PubMed

Enzalutamide monotherapy

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Regimen

Study Evidence Efficacy
Traina et al. 2018 Phase II CBR @ 16 wks: 25% (95% CI 17-33)

Patients had AR-positive TNBC.

Endocrine therapy

Continued until progression

References

  1. Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 2018 Mar 20;36(9):884-890. Epub 2018 Jan 26. link to original article contains verified protocol PubMed

Investigational agents

Drugs with some degree of promising activity in clinical trials.