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Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

Authors Hollis RL, Churchman M, Gourley C

Received 14 December 2016

Accepted for publication 9 March 2017

Published 11 May 2017 Volume 2017:10 Pages 2539—2551

DOI https://doi.org/10.2147/OTT.S102569

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Jianmin Xu

Robert L Hollis, Michael Churchman, Charlie Gourley

Nicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK

Abstract: Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes BRCA1 or BRCA2 (BRCA). BRCA1- and BRCA2-associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the “BRCAness” phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that BRCA1- and BRCA2-associated OCs display distinct characteristics, most notably in long-term patient survival. Furthermore, recent data indicate that the site of BRCA1 mutation is important with regard to platinum and PARP inhibitor sensitivity. Here, we summarize the body of research describing the BRCAness phenotype and highlight the differential implications of different BRCA mutations with regard to clinicopathologic features, therapy sensitivity and clinical outcome in OC.

Keywords: ovarian cancer, BRCA1, BRCA2, BRCAness

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