Mutations in BRCA1 or BRCA2 define a subset of prostate cancer patients. Herein, we address the question whether BRCA1/2 mutations have a predictive impact on chemotherapy with docetaxel, a widely used drug in patients with metastatic castration resistant prostate cancer (mCRPC). Fifty-three men treated with docetaxel for mCRPC were tested for somatic BRCA1/2 mutations of the primary tumor. In a subgroup of patients, BRCA1/2 protein expression was tested as a potential surrogate marker for BRCA1/2 inactivation. Eight of 53 patients (15.1%) harbored a deleterious BRCA2 mutation. No BRCA1 mutation was found. Patients with a BRCA2 mutation showed a response rate of 25% to docetaxel in comparison to 71.1% in men with wildtype BRCA2 (p = 0.019). While the time to develop castration resistance was similar in both subgroups, the overall survival was significantly shorter in patients harboring a BRCA2 mutation. No correlation between the BRCA1/2 protein expression and the response to docetaxel was found. While the presence of a BRCA2 mutation does not preclude a response to docetaxel, there is overall a significant correlation between BRCA2 inactivation and a poor response rate. Our results suggest that a close oncological monitoring of patients with BRCA2 mutations for taxane resistance is warranted.
Mutations in BRCA2 and taxane resistance in prostate cancer
Cathleen Nientiedt,Martina Heller,V. Endris,A. Volckmar,S. Zschäbitz,M. Tapia-Laliena,A. Duensing,D. Jäger,P. Schirmacher,H. Sültmann,A. Stenzinger,M. Hohenfellner,C. Grüllich,S. Duensing
Published 2017 in Scientific Reports
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- Publication year
2017
- Venue
Scientific Reports
- Publication date
2017-07-04
- Fields of study
Medicine
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Semantic Scholar, PubMed
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