Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

Author:

Castro Elena1,Goh Chee1,Olmos David1,Saunders Ed1,Leongamornlert Daniel1,Tymrakiewicz Malgorzata1,Mahmud Nadiya1,Dadaev Tokhir1,Govindasami Koveela1,Guy Michelle1,Sawyer Emma1,Wilkinson Rosemary1,Ardern-Jones Audrey1,Ellis Steve1,Frost Debra1,Peock Susan1,Evans D. Gareth1,Tischkowitz Marc1,Cole Trevor1,Davidson Rosemarie1,Eccles Diana1,Brewer Carole1,Douglas Fiona1,Porteous Mary E.1,Donaldson Alan1,Dorkins Huw1,Izatt Louise1,Cook Jackie1,Hodgson Shirley1,Kennedy M. John1,Side Lucy E.1,Eason Jacqueline1,Murray Alex1,Antoniou Antonis C.1,Easton Douglas F.1,Kote-Jarai Zsofia1,Eeles Rosalind1

Affiliation:

1. Elena Castro, Chee Goh, Ed Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Nadiya Mahmud, Tokhir Dadaev, Koveela Govindasami, Michelle Guy, Emma Sawyer, Rosemary Wilkinson, Zsofia Kote-Jarai, and Rosalind Eeles, Institute of Cancer Research; Elena Castro, Chee Goh, Audrey Ardern-Jones, and Rosalind Eeles, Royal Marsden National Health Service (NHS) Foundation Trust; Louise Izatt, Guy's and St Thomas' NHS Foundation Trust; Shirley Hodgson, St George's, University of London; Lucy E. Side, Great...

Abstract

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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