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Sci Rep. 2017 Jul 4;7(1):4574. doi: 10.1038/s41598-017-04897-x.

Mutations in BRCA2 and taxane resistance in prostate cancer.

Author information

1
Molecular Urooncology, Department of Urology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 517, D-69120, Heidelberg, Germany.
2
Department of Medical Oncology, University of Heidelberg School of Medicine, National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, D-69120, Heidelberg, Germany.
3
Department of Pathology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 224, D-69120, Heidelberg, Germany.
4
Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
5
Cancer Genome Research, National Center for Tumor Diseases, German Cancer Research Center and German Cancer Consortium (DKTK), Im Neuenheimer Feld 460, D-69120, Heidelberg, Germany.
6
Department of Urology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany.
7
Molecular Urooncology, Department of Urology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 517, D-69120, Heidelberg, Germany. stefan.duensing@med.uni-heidelberg.de.
8
Department of Urology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany. stefan.duensing@med.uni-heidelberg.de.

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.

PMID:
28676659
PMCID:
PMC5496866
DOI:
10.1038/s41598-017-04897-x
[Indexed for MEDLINE]
Free PMC Article

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