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Mutations in BRCA2 and taxane resistance in prostate cancer

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 tre...

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Main Authors: Nientiedt, Cathleen (Author) , Heller, Martina (Author) , Endris, Volker (Author) , Volckmar, Anna-Lena (Author) , Zschäbitz, Stefanie (Author) , Tapia-Laliena, María Angeles (Author) , Jäger, Dirk (Author) , Schirmacher, Peter (Author) , Sültmann, Holger (Author) , Stenzinger, Albrecht (Author) , Hohenfellner, Markus (Author) , Grüllich, Carsten (Author) , Duensing, Stefan (Author)
Format: Article (Journal)
Language:English
Published: 4 July 2017
In: Scientific reports
Year: 2017, Volume: 7
ISSN:2045-2322
DOI:10.1038/s41598-017-04897-x
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/s41598-017-04897-x
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-017-04897-x
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Author Notes: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

MARC

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520 |a 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. 
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