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

Fasching P, Loibl S, Hu C, Hart SN, Shimelis H, Moore R, Schem C, Tesch H, Untch M, Hilfrich J, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm T, Huober J, Liedtke C, Weinshilboum RM, Wang L, Ingle JN, Mueller V, Nekljudova V, Weber KE, Rack B, Rübner M, Von Minckwitz G, Couch FJ (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of Clinical Oncology American Society of Clinical Oncology

Book Volume: 36

Pages Range: 2281-2287

Journal Issue: 22

DOI: 10.1200/JCO.2017.77.2285

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 with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe Matthias Rübner Medizinische Fakultät

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universität Rostock DE Germany (DE) Mayo Clinic US United States (USA) (US) Luisenkrankenhaus Düsseldorf DE Germany (DE) GBG Forschungs GmbH (German Breast Group) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universität Ulm DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Centrum für Hämatologie und Onkologie Bethanien DE Germany (DE) Eilenriede Klinik Hannover DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) HELIOS Kliniken DE Germany (DE) Universitätsklinikum Magdeburg A.ö.R. DE Germany (DE)

How to cite

APA:

Fasching, P., Loibl, S., Hu, C., Hart, S.N., Shimelis, H., Moore, R.,... Couch, F.J. (2018). 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. Journal of Clinical Oncology, 36(22), 2281-2287. https://doi.org/10.1200/JCO.2017.77.2285

MLA:

Fasching, Peter, et al. "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." Journal of Clinical Oncology 36.22 (2018): 2281-2287.

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