Breast Cancer Research and Treatment

, Volume 142, Issue 3, pp 549–558 | Cite as

Superior outcome after neoadjuvant chemotherapy with docetaxel, anthracycline, and cyclophosphamide versus docetaxel plus cyclophosphamide: results from the NATT trial in triple negative or HER2 positive breast cancer

  • Xiaosong Chen
  • Guolin Ye
  • Chenfang Zhang
  • Xinzheng Li
  • Yiding Chen
  • Xiaohong Xie
  • Hong Zheng
  • Yali Cao
  • Kejin Wu
  • Duo Ni
  • Jinhai Tang
  • Ziguo Wei
  • Kunwei Shen
Clinical trial


The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide (TC) compared with docetaxel, anthracycline, and cyclophosphamide (TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3–36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event-free survival (adjusted hazard ratio [HR] 2.42; 95 % CI 1.11–5.30) and disease-free survival (HR 2.85; 95 % CI 1.21–6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation.


Triple negative breast cancer Neoadjuvant chemotherapy Anthracycline Pathological complete remission Prognosis HER2 positive breast cancer 


  1. 1.
    DeSantis C, Siegel R, Bandi P et al (2011) Breast cancer statistics. CA Cancer J Clin 61(6):409–418PubMedGoogle Scholar
  2. 2.
    Kaufmann M, von Minckwitz G, Bear HD et al (2007) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol 18:1927–1934PubMedCrossRefGoogle Scholar
  3. 3.
    Fumagalli D, Bedard PL, Nahleh Z et al (2012) A common language in neoadjuvant breast cancer clinical trials: proposals for standard definitions and endpoints. Lancet Oncol 13(6):e240–e248PubMedCrossRefGoogle Scholar
  4. 4.
    Mauri D, Pavlidis N, Ioannidis JP (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 7:188–194CrossRefGoogle Scholar
  5. 5.
    Rastogi P, Anderson S, Bear HD et al (2008) Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol 26:778–785PubMedCrossRefGoogle Scholar
  6. 6.
    Berruti A, Generali D, Kaufmann M et al (2011) International expert consensus on primary systemic therapy in the management of early breast cancer: highlights of the fourth symposium on primary systemic therapy in the management of operable breast cancer, Cremona, Italy (2010). J Natl Cancer Inst Monogr 2011(43):147–151PubMedCrossRefGoogle Scholar
  7. 7.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444CrossRefGoogle Scholar
  8. 8.
    Smith IC, Heys SD, Hutcheon AW et al (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20(6):1456–1466PubMedCrossRefGoogle Scholar
  9. 9.
    Mackey JR, Martin M, Pienkowski T et al (2013) Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol 14(1):72–80PubMedCrossRefGoogle Scholar
  10. 10.
    Martín M, Seguí MA, Antón A et al (2010) Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 363(23):2200–2210PubMedCrossRefGoogle Scholar
  11. 11.
    von Minckwitz G, Kümmel S, Vogel P et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100(8):552–562CrossRefGoogle Scholar
  12. 12.
    Aebi S, Davidson T, Gruber G et al (2011) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi12–24PubMedGoogle Scholar
  13. 13.
    Dhesy-Thind B, Pritchard KI, Messersmith H et al (2008) HER2/neu in systemic therapy for women with breast cancer: a systematic review. Breast Cancer Res Treat 109(2):209–229PubMedCrossRefGoogle Scholar
  14. 14.
    Gennari A, Sormani MP, Pronzato P et al (2008) HER-2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100:14–20PubMedCrossRefGoogle Scholar
  15. 15.
    Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283PubMedCrossRefGoogle Scholar
  16. 16.
    Jones SE, Savin MA, Holmes FA et al (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387PubMedCrossRefGoogle Scholar
  17. 17.
    Chen XS, Nie XQ, Chen CM et al (2010) Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer. Ann Oncol 21(5):961–967PubMedCrossRefGoogle Scholar
  18. 18.
    Wildiers H, Neven P, Christiaens MR et al (2011) Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer. Ann Oncol 22(3):588–594PubMedCrossRefGoogle Scholar
  19. 19.
    Burstein HJ, Piccart-Gebhart MJ, Perez EA et al (2012) Choosing the best trastuzumab-based adjuvant chemotherapy regimen: should we abandon anthracyclines? J Clin Oncol 30(18):2179–2182PubMedCrossRefGoogle Scholar
  20. 20.
    Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRefGoogle Scholar
  21. 21.
    Goldhirsch A, Wood WC, Coates AS et al (2011) Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747PubMedCrossRefGoogle Scholar
  22. 22.
    Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16):5678–5685PubMedCrossRefGoogle Scholar
  23. 23.
    Carey LA, Dees EC, Sawyer L et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334PubMedCrossRefGoogle Scholar
  24. 24.
    Singletary SE, Connolly JL (2006) Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J Clin 56(1):37–47PubMedCrossRefGoogle Scholar
  25. 25.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247PubMedCrossRefGoogle Scholar
  26. 26.
    Gianni L, Eiermann W, Semiglazov V et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 375(9712):377–384PubMedCrossRefGoogle Scholar
  27. 27.
    Hudis CA, Barlow WE, Costantino JP et al (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25(15):2127–2132PubMedCrossRefGoogle Scholar
  28. 28.
    Huober J, von Minckwitz G, Denkert C et al (2010) Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124(1):133–140PubMedCrossRefGoogle Scholar
  29. 29.
    Berry DA (2009) Monitoring accumulating data in a clinical trial. Biometrics 45:1197–1211CrossRefGoogle Scholar
  30. 30.
    Khasraw M, Bell R, Dang C (2012) Epirubicin: is it like doxorubicin in breast cancer? A clinical review. Breast 21(2):142–149PubMedCrossRefGoogle Scholar
  31. 31.
    Caudle AS, Gonzalez-Angulo AM, Hunt KK et al (2010) Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28(11):1821–1828PubMedCrossRefGoogle Scholar
  32. 32.
    Ellis P, Barrett-Lee P, Johnson L et al (2009) Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet 373(9676):1681–1692PubMedCrossRefGoogle Scholar
  33. 33.
    Burnell MJ, Levine MN, Chapman JA et al (2007) A phase III adjuvant trial of sequenced EC + filgrastim + epoetin-alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node-positive or high-risk node-negative breast cancer (NCIC CTG MA.21). J Clin Oncol 25(suppl 18):550Google Scholar
  34. 34.
  35. 35.
    von Minckwitz G, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15):1796–1804CrossRefGoogle Scholar
  36. 36.
    Gianni L, Dafni U, Gelber RD et al (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12(3):236–244PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xiaosong Chen
    • 1
  • Guolin Ye
    • 2
  • Chenfang Zhang
    • 3
  • Xinzheng Li
    • 4
  • Yiding Chen
    • 5
  • Xiaohong Xie
    • 6
  • Hong Zheng
    • 7
  • Yali Cao
    • 8
  • Kejin Wu
    • 9
  • Duo Ni
    • 10
  • Jinhai Tang
    • 11
  • Ziguo Wei
    • 12
  • Kunwei Shen
    • 1
  1. 1.Comprehensive Breast Health Center, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of Breast SurgeryThe First People’s Hospital of FoshanFoshanChina
  3. 3.Department of Breast SurgeryGuangzhou General Hospital of Guangzhou Military AreaGuangzhouChina
  4. 4.Department of Breast SurgeryShanxi Provincial Cancer HospitalTaiyuanChina
  5. 5.Department of Breast SurgeryObstetrics and Gynecology Hospital Affiliated to Zhejiang UniversityHangzhouChina
  6. 6.Department of Breast SurgeryZhejiang Traditional Chinese Medical HospitalHangzhouChina
  7. 7.Department of Breast SurgeryWest China Hospital Sichuan UniversityChengduChina
  8. 8.Department of Breast SurgeryThe Third Hospital of NanchangNanchangChina
  9. 9.Department of Breast Surgery, Xin Hua HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  10. 10.Department of Breast SurgeryXinjiang Uygur Autonomous Region Cancer HospitalXinjiangChina
  11. 11.Department of Breast SurgeryJiangsu Cancer HospitalNanjingChina
  12. 12.Department of Breast and Thyroid SurgeryLinyi People’s HospitalLinyiChina

Personalised recommendations