Mutations in BRCA2 and taxane resistance in prostate cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

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. More... »

PAGES

4574

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-04897-x

DOI

http://dx.doi.org/10.1038/s41598-017-04897-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090342911

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28676659


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