Peter A. Fasching and Matthias Rübner, Erlangen University Hospital, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen; Sibylle Loibl, Valentina Nekljudova, Karsten E. Weber, and Gunter von Minckwitz, German Breast Group Forschungs, Neu-Isenburg; Christian Schem, University Medical Center Schleswig-Holstein, Kiel; Hans Tesch, Centrum für Hämatologie und Onkologie Bethanien, Frankfurt; Michael Untch, Helios-Klinikum, Berlin-Buch; Jörn Hilfrich, Eilenriede-Klinik, Hannover; Mahdi Rezai, Luisenkrankenhaus; Tanja Fehm, Düsseldorf University Hospital, Heinrich-Heine University of Düsseldorf, Düsseldorf; Bernd Gerber, University of Rostock, Rostock; Serban Dan Costa, Magdeburg University Hospital, Magdeburg; Jens-Uwe Blohmer and Cornelia Liedtke, Charité University Hospital Campus Charité-Mitte, Berlin; Jens Huober, University of Ulm; Brigitte Rack, University Hospital Ulm, Ulm; Volkmar Müller, Hamburg University Hospital, Hamburg, Germany; Chunling Hu, Steven N. Hart, Hermela Shimelis, Raymond Moore, James N. Ingle, and Fergus J. Couch, Mayo Clinic; and Richard M. Weinshilboum and Liewei Wang, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN.
J Clin Oncol. 2018 Aug 1;36(22):2281-2287. doi: 10.1200/JCO.2017.77.2285. Epub 2018 May 23.
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.
目的 BRCA1/2 突变在三阴性乳腺癌(TNBC)患者中很常见。这些患者通常接受初始系统化疗。本研究的目的是分析在蒽环类和紫杉烷类化疗联合或不联合贝伐珠单抗治疗的 TNBC 患者中,BRCA1/2 突变对病理完全缓解(pCR)和无病生存(DFS)的影响。
方法 对来自 GeparQuinto 研究的 493 例 TNBC 患者的种系 DNA 进行测序,以鉴定 BRCA1 和 BRCA2 中的突变。比较突变患者与无突变患者、贝伐珠单抗治疗患者与无贝伐珠单抗治疗患者的 pCR 率。此外,还评估了 BRCA1/2 突变状态和 pCR 状态对治疗相关 DFS 的影响。
结果 在 18.3%的 TNBC 患者中检测到 BRCA1/2 突变。总体而言,突变患者的 pCR 率为 50%,而无突变患者的 pCR 率为 31.5%(比值比 [OR],2.17;95%CI,1.37 至 3.46;P =.001)。贝伐珠单抗治疗的 BRCA1/2 突变携带者的 pCR 率为 61.5%,而无突变的患者为 35.6%(OR,2.90;95%CI,1.43 至 5.89;P =.004)。对于无 BRCA1/2 突变的患者,pCR 是 DFS 的强有力预测因素(危险比,0.18;95%CI,0.11 至 0.31),但对于有 BRCA1/2 突变的患者并非如此(危险比,0.74;95%CI,0.32 至 1.69)。
结论 在 BRCA1/2 突变的 TNBC 患者中,添加贝伐珠单抗可能会增加标准新辅助化疗后的 pCR。在接受蒽环类和紫杉烷类化疗(联合或不联合贝伐珠单抗)的患者中,pCR 对 BRCA1/2 突变携带者的 DFS 预测作用弱于无突变患者。