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

被引:79
作者
Fasching, Peter A. [1 ]
Loibl, Sibylle [2 ]
Hu, Chunling [15 ]
Hart, Steven N. [15 ]
Shimelis, Hermela [15 ]
Moore, Raymond [15 ]
Schem, Christian [3 ]
Tesch, Hans [4 ]
Untch, Michael [5 ]
Hilfrich, Joern [6 ]
Rezai, Mahdi [7 ]
Gerber, Bernd [9 ]
Costa, Serban Dan [10 ]
Blohmer, Jens-Uwe [11 ]
Fehm, Tanja [8 ]
Huober, Jens [12 ]
Liedtke, Cornelia [11 ]
Weinshilboum, Richard M. [16 ]
Wang, Liewei [16 ]
Ingle, James N. [15 ]
Mueller, Volkmar [14 ]
Nekljudova, Valentina [2 ]
Weber, Karsten E. [2 ]
Rack, Brigitte [13 ]
Ruebner, Matthias [1 ]
von Minckwitz, Gunter [2 ]
Couch, Fergus J. [15 ]
机构
[1] Friedrich Alexander Univ Erlangen Nuremberg, Erlangen Univ Hosp, Erlangen, Germany
[2] German Breast Grp Forsch, Neu Isenburg, Germany
[3] Univ Med Ctr Schleswig Holstein, Kiel, Germany
[4] Ctr Hamatol & Onkol Bethanien, Frankfurt, Germany
[5] HELIOS Klin, Berlin, Germany
[6] Eilenriede Klin, Hannover, Germany
[7] Luisenkrankenhaus, Dusseldorf, Germany
[8] Heinrich Heine Univ Dusseldorf, Dusseldorf Univ Hosp, Dusseldorf, Germany
[9] Univ Rostock, Rostock, Germany
[10] Magdeburg Univ Hosp, Magdeburg, Germany
[11] Charite, Campus Charite Mitte, Berlin, Germany
[12] Univ Ulm, Ulm, Germany
[13] Univ Hosp Ulm, Ulm, Germany
[14] Hamburg Univ Hosp, Hamburg, Germany
[15] Mayo Clin, Rochester, MN USA
[16] Mayo Clin, Coll Med, Mayo Fdn, Rochester, MN USA
基金
美国国家卫生研究院;
关键词
PATHOLOGICAL COMPLETE RESPONSE; TAXANE-BASED CHEMOTHERAPY; SYNTHETIC LETHALITY; DOWN-REGULATION; CARRIERS; PACLITAXEL; EVEROLIMUS; SURVIVAL; THERAPY; PHASE-3;
D O I
10.1200/JCO.2017.77.2285
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PurposeBRCA1/2 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 MethodsGermline 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.ResultsBRCA1/2 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).ConclusionThe 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.
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页码:2281 / +
页数:12
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