Title |
Mutations in BRCA2 and taxane resistance in prostate cancer
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Published in |
Scientific Reports, July 2017
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DOI | 10.1038/s41598-017-04897-x |
Pubmed ID | |
Authors |
Cathleen Nientiedt, Martina Heller, Volker Endris, Anna-Lena Volckmar, Stefanie Zschäbitz, María A. Tapia-Laliena, Anette Duensing, Dirk Jäger, Peter Schirmacher, Holger Sültmann, Albrecht Stenzinger, Markus Hohenfellner, Carsten Grüllich, Stefan Duensing |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | 25% |
United States | 1 | 25% |
Unknown | 2 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 75% |
Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 42 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 17% |
Student > Master | 5 | 12% |
Student > Bachelor | 3 | 7% |
Researcher | 3 | 7% |
Professor > Associate Professor | 2 | 5% |
Other | 5 | 12% |
Unknown | 17 | 40% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 31% |
Biochemistry, Genetics and Molecular Biology | 5 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Agricultural and Biological Sciences | 2 | 5% |
Arts and Humanities | 1 | 2% |
Other | 2 | 5% |
Unknown | 17 | 40% |