医学
卡铂
乳腺癌
肿瘤科
内科学
三阴性乳腺癌
种系突变
紫杉烷
养生
BRCA突变
癌症
突变
化疗
遗传学
生物
顺铂
基因
作者
Eric Hahnen,Bianca Lederer,Jan Hauke,Sibylle Loibl,Sandra Kröber,Andreas Schneeweiß,Carsten Denkert,Peter A. Fasching,Jens-Uwe Blohmer,Christian Jackisch,Stefan Paepke,Bernd Gerber,Sherko Kümmel,Christian Schem,Guido Neidhardt,Jens Huober,Kerstin Rhiem,Serban Dan Costa,Janine Altmüller,Claus Hanusch,Holger Thiele,Volkmar Müller,Peter Nürnberg,Thomas Karn,Valentina Nekljudova,Michael Untch,Gϋnter von Minckwitz,Rita K. Schmutzler
出处
期刊:JAMA Oncology
[American Medical Association]
日期:2017-10-01
卷期号:3 (10): 1378-1378
被引量:299
标识
DOI:10.1001/jamaoncol.2017.1007
摘要
Importance
The GeparSixto trial provided evidence that the addition of neoadjuvant carboplatin to a regimen consisting of anthracycline, taxane, and bevacizumab increases pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). WhetherBRCA1andBRCA2germline mutation status affects treatment outcome remains elusive. Objective
To determine whetherBRCA1andBRCA2germline mutation status affects therapy response in patients with TNBC. Design, Setting, and Participants
This secondary analysis of a randomized clinical trial used archived DNA samples and cancer family history of 315 patients with TNBC enrolled between August 1, 2011, and December 31, 2012, in the GeparSixto trial. In all, 291 participants (92.4%) were included in this multicenter prospective investigation. DNA samples were analyzed for germline mutations inBRCA1, BRCA2,and 16 other cancer predisposition genes. The pCR rates between the carboplatin and noncarboplatin arms were compared. Genetic analyses were performed at the Center for Familial Breast and Ovarian Cancer in Cologne, Germany; data analysis, November 1 through December 31, 2015. Main Outcomes and Measures
Proportion of patients who achieved pCR and disease-free survival after neoadjuvant treatment according toBRCA1andBRCA2germline mutation status. For pCR rates, the ypT0/is ypN0 definition was used as a primary end point. Results
Of the 291 patients with TNBC, all were women; the mean (SD) age was 48 (11) years. The pCR rate in the carboplatin group was 56.8% (83 of 146) and 41.4% (60 of 145) in the noncarboplatin group (odds ratio [OR], 1.87; 95% CI, 1.17-2.97;P = .009). PathogenicBRCA1andBRCA2germline mutations were present in 50 of the 291 patients (17.2%). In the noncarboplatin arm, the pCR rate was 66.7% (16 of 24) for patients withBRCA1andBRCA2mutations and 36.4% (44 of 121) for patients without (OR, 3.50; 95% CI, 1.39-8.84;P = .008). The high pCR rate observed inBRCA1andBRCA2mutation carriers (16 of 24 [66.7%]) was not increased further by adding carboplatin (17 of 26 [65.4%]). In contrast, carboplatin increased response rates in patients withoutBRCA1andBRCA2mutations: 66 of the 120 patients (55%) withoutBRCA1andBRCA2mutations achieved pCR in the carboplatin arm vs 44 of the 121 patients (36.4%) in the noncarboplatin arm (OR, 2.14; 95% CI, 1.28-3.58;P = .004). Patients without pathogenicBRCA1andBRCA2alterations showed elevated disease-free survival rates when carboplatin was added (without carboplatin, 73.5%; 95% CI, 64.1%-80.8% vs with carboplatin, 85.3%; 95% CI, 77.0%-90.8%; hazard ratio, 0.53; 95% CI, 0.29-0.96;P = .04). Conclusions and Relevance
Under the nonstandard GeparSixto polychemotherapy regimen, patients withoutBRCA1andBRCA2germline mutations benefited from the addition of carboplatin and those withBRCA1andBRCA2mutations showed superior response rates without additive effects observed for carboplatin. Trial Registration
clinicaltrials.gov Identifier:NCT01426880