BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study.

Abstract

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

• Authors: Peter A Fasching, Sibylle Loibl, Chunling Hu, Steven N Hart, Hermela Shimelis, Raymond Moore, Christian Schem, Hans Tesch, Michael Untch, Jörn Hilfrich, Mahdi Rezai, Bernd Gerber, Serban Dan Costa, Jens-Uwe Blohmer, Tanja Fehm, Jens Huober, Cornelia Liedtke, Richard M Weinshilboum, Liewei Wang, James N Ingle, Volkmar Müller, Valentina Nekljudova, Karsten E Weber, Brigitte Rack, Matthias Rübner, Gunter von Minckwitz, Fergus J Couch
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 36 Issue 22 Pg. 2281-2287 (08 01 2018) ISSN: 1527-7755 [Electronic] United States
• PMID: 29791287 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Docetaxel
• Bevacizumab
• Epirubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Bevacizumab (administration & dosage)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Docetaxel (administration & dosage)
• Epirubicin (administration & dosage)
• Female
• Genotype
• Germ-Line Mutation
• Humans
• Neoadjuvant Therapy
• Receptor, ErbB-2 (metabolism)
• Triple Negative Breast Neoplasms (blood, drug therapy, genetics, pathology)