Optimizing Adjuvant and Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

  • Sonya Reid-Lawrence
  • Antoinette R. Tan
  • Ingrid A. MayerEmail author


The mainstay of treatment for early-stage and locally advanced triple-negative breast cancer (TNBC) is chemotherapy. Anthracycline−/alkylator- and taxane-based regimens are considered the standard of care for the systemic treatment of high-risk triple-negative disease. Common approaches include sequential anthracycline/alkylator followed by taxane or concurrent delivery of an anthracycline, an alkylator, and a taxane. Shorter courses of treatment are considered appropriate for lower-risk triple-negative, node-negative tumors less than 1 cm. Despite treatment with anthracycline- and taxane-based chemotherapy regimens, about 30% of early-stage TNBC develop recurrent and metastatic disease, and many efforts are focused on how to optimize our current neoadjuvant and adjuvant approaches. Incorporation of platinum agents in the neoadjuvant setting appears promising, but long-term outcome data are needed. Treatment of high residual disease burden with additional chemotherapy after completion of neoadjuvant therapy is becoming an important area of investigation. The hope is that newer biologically driven strategies and development of biomarkers will lead to more effective and individualized therapy for TNBC.


Triple-negative breast cancer Basal-like breast cancer Adjuvant therapy Neoadjuvant chemotherapy 


  1. 1.
    Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.CrossRefPubMedGoogle Scholar
  2. 2.
    Millikan RC, Newman B, Tse CK, et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat. 2008;109:123–39.CrossRefPubMedGoogle Scholar
  3. 3.
    Carey LA, Dees EC, Sawyer L, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.CrossRefPubMedGoogle Scholar
  4. 4.
    Early Breast Cancer Trialists’ Collaborative G, Clarke M, Coates AS, et al. Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet. 2008;371:29–40.CrossRefGoogle Scholar
  5. 5.
    Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006;295:1658–67.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Killelea BK, Yang VQ, Mougalian S, et al. Neoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the national cancer database. J Am Coll Surg. 2015;220:1063–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and bowel project protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMedGoogle Scholar
  8. 8.
    von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRefGoogle Scholar
  9. 9.
    Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Jones RL, Salter J, A’Hern R, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2009;116:53–68.CrossRefPubMedGoogle Scholar
  11. 11.
    Guarneri V, Piacentini F, Ficarra G, et al. A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy. Ann Oncol. 2009;20:1193–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the cancer care Ontario clinical practice guideline. J Clin Oncol. 2016;34:2416–27.CrossRefPubMedGoogle Scholar
  13. 13.
    National Comprehensive Cancer Network. Breast cancer (Version 2.2017-April 6, 2017). Accessed 27 Aug 2017.
  14. 14.
    Swain SM, Jeong JH, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010;362:2053–65.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sparano JA, Zhao F, Martino S, et al. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015;33:2353–60.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hayes DF, Thor AD, Dressler LG, et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med. 2007;357:1496–506.CrossRefPubMedGoogle Scholar
  17. 17.
    Martin M, Rodriguez-Lescure A, Ruiz A, et al. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010;123:149–57.CrossRefPubMedGoogle Scholar
  18. 18.
    Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Hugh J, Hanson J, Cheang MC, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27:1168–76.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Martin M, Segui MA, Anton A, et al. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010;363:2200–10.CrossRefPubMedGoogle Scholar
  21. 21.
    Swain SM, Tang G, Geyer CE Jr, et al. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013;31:3197–204.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Budd GT, Barlow WE, Moore HC, et al. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015;33:58–64.CrossRefPubMedGoogle Scholar
  23. 23.
    Bell R, Brown J, Parmar M, et al. Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer. Ann Oncol. 2017;28:754–60.PubMedGoogle Scholar
  24. 24.
    Martin M, Rodriguez-Lescure A, Ruiz A, et al. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008;100:805–14.CrossRefPubMedGoogle Scholar
  25. 25.
    Ho AY, Gupta G, King TA, et al. Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy. Cancer. 2012;118:4944–52.CrossRefPubMedGoogle Scholar
  26. 26.
    Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24:5381–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Cheang MC, Voduc KD, Tu D, et al. Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the NCIC.CTG MA.5 randomized trial. Clin Cancer Res. 2012;18:2402–12.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Colleoni M, Cole BF, Viale G, et al. Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol. 2010;28:2966–73.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Harbeck N, Gluz O, Clemens MR, et al. Prospective WSG phase III PlanB trial: Final analysis of adjuvant 4 x EC→4 x docetaxel vs. 6 x docetaxel/cyclophosphamide in patients with high clinical risk and intermediate-to-high genomic risk HER2-negative, early breast cancer. J Clin Oncol. 35 suppl (abstract 504), 2017.Google Scholar
  30. 30.
    Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: the ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647–55.CrossRefPubMedGoogle Scholar
  31. 31.
    Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefPubMedGoogle Scholar
  32. 32.
    Bertucci F, Finetti P, Cervera N, et al. How basal are triple-negative breast cancers? Int J Cancer. 2008;123:236–40.CrossRefPubMedGoogle Scholar
  33. 33.
    Matros E, Wang ZC, Lodeiro G, et al. BRCA1 promoter methylation in sporadic breast tumors: relationship to gene expression profiles. Breast Cancer Res Treat. 2005;91:179–86.CrossRefPubMedGoogle Scholar
  34. 34.
    Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer. 2004;4:814–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235–44.CrossRefPubMedGoogle Scholar
  36. 36.
    Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2009;115:359–63.CrossRefPubMedGoogle Scholar
  37. 37.
    Byrski T, Huzarski T, Dent R, et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2014;147:401–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28:1145–53.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ryan PD, Tung NM, Isakoff SJ, et al. Neoadjuvant cisplatin and bevacizumab in triple-negative breast cancer: Safety and efficacy. J Clin Oncol. 2009;27 suppl (abstract 551).Google Scholar
  40. 40.
    von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15:747–56.CrossRefGoogle Scholar
  41. 41.
    Sikov WM, Berry DA, Perou CM, et al. 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;33:13–21.CrossRefPubMedGoogle Scholar
  42. 42.
    Prowell TM, Pazdur R. Pathological complete response and accelerated drug approval in early breast cancer. N Engl J Med. 2012;366:2438–41.CrossRefPubMedGoogle Scholar
  43. 43.
    Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMedGoogle Scholar
  44. 44.
    Sharma P, Lopez-Tarruella S, Garcia-Saenz JA, et al. Efficacy of neoadjuvant carboplatin plus docetaxel in triple-negative breast cancer: combined analysis of two cohorts. Clin Cancer Res. 2017;23:649–57.CrossRefPubMedGoogle Scholar
  45. 45.
    Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147–59.CrossRefPubMedGoogle Scholar
  46. 46.
    Midgley R, Kerr DJ. Capecitabine: have we got the dose right? Nat Clin Pract Oncol. 2009;6:17–24.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Sonya Reid-Lawrence
    • 1
  • Antoinette R. Tan
    • 2
  • Ingrid A. Mayer
    • 1
    Email author
  1. 1.Division of Hematology/OncologyVanderbilt University Medical Center, Vanderbilt-Ingram Cancer CenterNashvilleUSA
  2. 2.Department of Solid Tumor Oncology and Investigational TherapeuticsLevine Cancer Institute, Carolinas HealthCare SystemCharlotteUSA

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