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Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis

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Abstract

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR + HER-2−; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p = 0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

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References

  1. Estevez LG, Gradishar WJ. Evidence-based use of neoadjuvant taxane in operable and inoperable breast cancer. Clin Cancer Res. 2004;10:3249–61.

    Article  PubMed  CAS  Google Scholar 

  2. Kaufmann M, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24:1940–9.

    Article  PubMed  Google Scholar 

  3. Fisher B, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from national surgical adjuvant breast and bowel project B-18. J Clin Oncol. 1997;15:2483–93.

    PubMed  CAS  Google Scholar 

  4. Fisher B, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672–85.

    PubMed  CAS  Google Scholar 

  5. van der Hage JA, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.

    PubMed  Google Scholar 

  6. Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94.

    Article  PubMed  Google Scholar 

  7. Chevallier B, Roche H, Olivier JP, Chollet P, Hurteloup P. Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in high histologic response rate. Am J Clin Oncol. 1993;16:223–8.

    Article  PubMed  CAS  Google Scholar 

  8. Chollet P, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer. 2002;86:1041–6.

    Article  PubMed  CAS  Google Scholar 

  9. Bear HD, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project protocol B-27. J Clin Oncol. 2006;24:2019–27.

    Article  PubMed  CAS  Google Scholar 

  10. Machiavelli MR, et al. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am. 1998;4:125–31.

    PubMed  CAS  Google Scholar 

  11. Thomas E, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004;22:2294–302.

    Article  PubMed  CAS  Google Scholar 

  12. Kuerer HM, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.

    PubMed  CAS  Google Scholar 

  13. Citron ML, et al. Randomized trial, of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of intergroup trial C9741/cancer and leukemia group B trial 9741. J Clin Oncol. 2003;21:1431–9.

    Article  PubMed  CAS  Google Scholar 

  14. Green MC, et al. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel with paclitaxel once every 3 weeks. J Clin Oncol. 2005;23:5983–92.

    Article  PubMed  CAS  Google Scholar 

  15. Melichar B, et al. Urinary neopterin, hemoglobin and peripheral blood cell counts in breast carcinoma patients treated with dose-dense chemotherapy. Anticancer Res. 2008;28:2389–96.

    PubMed  CAS  Google Scholar 

  16. Hornychova H, et al. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma. Cancer Invest. 2008;26:1024–31.

    Article  PubMed  CAS  Google Scholar 

  17. Straver ME, et al. The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy. Ann Surg Oncol. 2010;17:2411–8.

    Article  PubMed  CAS  Google Scholar 

  18. Bhargava R, et al. Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy. A single institutional experience with 358 cases. Cancer. 2010;116:1431–9.

    Article  PubMed  CAS  Google Scholar 

  19. Tan MC, et al. Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer. Am J Surg. 2009;198:520–5.

    Article  PubMed  Google Scholar 

  20. Jones RL, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119:315–23.

    Article  PubMed  CAS  Google Scholar 

  21. Faneyte IF, et al. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003;88:406–12.

    Article  PubMed  CAS  Google Scholar 

  22. Rouzier R, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.

    Article  PubMed  CAS  Google Scholar 

  23. Sorlie T, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.

    Article  PubMed  CAS  Google Scholar 

  24. Sotiriou C, et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA. 2003;100:10393–8.

    Article  PubMed  CAS  Google Scholar 

  25. Chang JC, et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet. 2003;362:362–9.

    Article  PubMed  CAS  Google Scholar 

  26. van de Vijver MJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.

    Article  PubMed  Google Scholar 

  27. Montagna E, et al. Pathological complete response after preoperative systemic therapy and biologic baseline features. Breast Cancer Res Treat. 2010;124:689–99.

    Article  PubMed  Google Scholar 

  28. Carey LA, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.

    Article  PubMed  CAS  Google Scholar 

  29. Liedtke C, et al. Response neoadjuvant therapy and long term survival in patients with triple negative breast cancer. J Clin Oncol. 2008;26:1275–81.

    Article  PubMed  Google Scholar 

  30. Kimmick GG, et al. Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944). Breast Cancer Res Treat. 2009;113:479–90.

    Article  PubMed  CAS  Google Scholar 

  31. Piccart-Gebhart MJ, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.

    Article  PubMed  CAS  Google Scholar 

  32. Romond EH, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.

    Article  PubMed  CAS  Google Scholar 

  33. Joensuu H, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809–20.

    Article  PubMed  CAS  Google Scholar 

  34. Buzdar AU, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23:3676–85.

    Article  PubMed  CAS  Google Scholar 

  35. Henderson IC, et al. Improved outcomes from adding sequential paclitaxel but not from the escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.

    Article  PubMed  CAS  Google Scholar 

  36. Mamounas EP, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–96.

    Article  PubMed  CAS  Google Scholar 

  37. Untch M, et al. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol. 2009;27:2938–45.

    Article  PubMed  Google Scholar 

  38. Untch M, et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel darbepoetin alfa in primary breast cancer-results at the time of surgery. Ann Oncol. 2011;22:1988–98.

    Article  PubMed  CAS  Google Scholar 

  39. von Minckwitz G, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23:2676–85.

    Article  Google Scholar 

  40. von Minckwitz G, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125:145–56.

    Article  Google Scholar 

  41. Bonilla L, et al. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst. 2010;102:1845–54.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported by the grant of the Internal Grant Agency of the Ministry of Health of the Czech Republic NS10286-3, Research Projects MZO 00179906 and MSM 6198959216.

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Authors and Affiliations

  1. Department of Oncology, Palacký University Medical School and Teaching Hospital, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic

    Bohuslav Melichar & Hana Kalábová

  2. Department of Oncology and Radiotherapy, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    Bohuslav Melichar & Hana Bašová

  3. Department of Pathology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    Helena Hornychová, Vladimír Červinka, Jan Laco & Aleš Ryška

  4. Department of Surgery, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    Jindřiška Mergancová & Pavel Jandík

  5. Department of Radiology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic

    Hana Urminská

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  1. Bohuslav Melichar
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  2. Helena Hornychová
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Correspondence to Bohuslav Melichar.

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Melichar, B., Hornychová, H., Kalábová, H. et al. Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis. Med Oncol 29, 2577–2585 (2012). https://doi.org/10.1007/s12032-012-0195-y

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  • DOI: https://doi.org/10.1007/s12032-012-0195-y

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