Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials
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Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.
KeywordsNeoadjuvant Breast cancer Pooled analysis Taxanes Anthracyclines trastuzumab
The pooled analysis was supported by Clinical Trials Unit (CTU) and University of Bern. The conduct of trials was supported by Amgen, Bristol Meyers Squibb, Roche, and Sanofi-Aventis, Germany by providing unrestricted grants and trial medication.
- 1.Peto R for the EBCTCG (2007) The worldwide overview updated (2005-6) meta-analysis of trial results. San Antonio Breast Cancer Symposium, Plenary Session Abstract 1Google Scholar
- 4.National Collaborating Centre for Cancer (2009) Early and locally advanced breast cancer: diagnosis and treatment. Velindre NHS Trust, CardiffGoogle Scholar
- 9.von Minckwitz G, Costa SD, Raab G et al (2001) Dose-dense doxorubicin and docetaxel with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol 19:3506–3515Google Scholar
- 10.von Minckwitz G, Raab G, Caputo A et al (2005) 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 23:2676–2685CrossRefGoogle Scholar
- 17.Untch M, Konecny G, Ditsch N et al (2002) Dose dense sequential epirubicin–paclitaxel as preoperative treatment of breast cancer: results of a randomised AGO study. Proc Am Soc Clin Oncol 21:34a (abstract 133)Google Scholar
- 18.Untch M, Stoeckl D, Konencny G et al (2005) A multicenter phase II study of preoperative epirubicin, cyclophosphamide (EC) followed by paclitaxel (P) plus trastuzumab (T) in Her2 positive primary breast cancer. San Antonio Breast Cancer Symposium (SABCS) 2005, abstract 1064Google Scholar
- 25.Buzdar AU, Ibrahim NK, Francis D et al (2005) 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 23:3676–3685CrossRefPubMedGoogle Scholar
- 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 375:377–384CrossRefPubMedGoogle Scholar
- 28.The Synergism or Long Duration (SOLD) Study. ClinicalTrials.gov Identifier: NCT00593697Google Scholar
- 29.PERSEPHONE—duration of trastuzumab study with chemotherapy in early breast cancer: six versus twelve months. ClinicalTrials.gov Identifier: NCT00712140Google Scholar