Mutations in BRCA2 and taxane resistance in prostate cancer

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-thre...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b15be919d5ff42faabf1b34d60384950
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spelling	oai:doaj.org-article:b15be919d5ff42faabf1b34d603849502021-12-02T12:31:51ZMutations in BRCA2 and taxane resistance in prostate cancer10.1038/s41598-017-04897-x2045-2322https://doaj.org/article/b15be919d5ff42faabf1b34d603849502017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04897-xhttps://doaj.org/toc/2045-2322Abstract 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.Cathleen NientiedtMartina HellerVolker EndrisAnna-Lena VolckmarStefanie ZschäbitzMaría A. Tapia-LalienaAnette DuensingDirk JägerPeter SchirmacherHolger SültmannAlbrecht StenzingerMarkus HohenfellnerCarsten GrüllichStefan DuensingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Mutations in BRCA2 and taxane resistance in prostate cancer
description	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.
format	article
author	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
author_facet	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
author_sort	Cathleen Nientiedt
title	Mutations in BRCA2 and taxane resistance in prostate cancer
title_short	Mutations in BRCA2 and taxane resistance in prostate cancer
title_full	Mutations in BRCA2 and taxane resistance in prostate cancer
title_fullStr	Mutations in BRCA2 and taxane resistance in prostate cancer
title_full_unstemmed	Mutations in BRCA2 and taxane resistance in prostate cancer
title_sort	mutations in brca2 and taxane resistance in prostate cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b15be919d5ff42faabf1b34d60384950
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Mutations in BRCA2 and taxane resistance in prostate cancer

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