Skip to content


Hereditary Cancer in Clinical Practice

Open Access

A multi-center study to evaluate the impact of germline BRCA1 and BRCA2 mutations on ovarian cancer survival

  • KL Bolton1,
  • G Chenevix-Trench2,
  • C Goh3,
  • S Sadetzki4, 5,
  • SJ Ramus6,
  • SA Gayther7,
  • SJ Chanock1,
  • AC Antoniou8 and
  • PDP Pharoah9
Hereditary Cancer in Clinical Practice201210(Suppl 2):A27

Published: 12 April 2012


Ovarian CancerCancer SurvivalMutation CarrierEpithelial Ovarian CancerGermline Mutation


Approximately 10 percent of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. However, the impact of these mutations on ovarian cancer prognosis remains unclear.


We performed an international multi-center study of 1,470 EOC cases with pathogenic germline mutations in BRCA1 (1,134) or BRCA2 (336) and 2,814 non-carriers. Our goal was to further characterize the survival of BRCA carriers with EOC compared to non-carriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Cox proportional hazards regression, both unadjusted and adjusted for other prognostic variables, was used to measure differences in overall survival during the five years following diagnosis.


The five-year overall survival was 36 percent for non-carriers, 44 percent for BRCA1 carriers and 52 percent for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 carriers showed a more favorable survival than non-carriers (BRCA1, HR=0.78; 95% CI=0.68-0.89, P=2x10-4; BRCA2, HR = 0.61; 95% CI=0.50-0.76, P=6x10-6;). These survival differences remained after adjustment for stage, grade, histology and age at diagnosis (BRCA1, HR=0.73, 95% CI=0.64-0.84, P=2x10-5; BRCA2, HR = 0.49, 95% CI=0.39-0.61, P=3x10-10).


We observed a significantly improved survival in germline BRCA1 and BRCA2 mutation carriers with EOC compared to non-carriers. BRCA2 carriers had the most favorable outcome with a distinct clinical course from BRCA1 carriers. The magnitude of the differences we observed highlight the need for clinical trials in EOC to be stratified by BRCA1/2 status and suggest that the routine testing of women presenting with high-grade serous EOC may be warranted.

Authors’ Affiliations

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA
Queensland Institute of Medical Research, Herston, Australia
Addenbrooke’s Hospital, Cambridge, UK
Cancer and Radiation Epidemiology Unit, Gertner Institute for Epidemiology and Health Policy, Sheba Medical Center, Tel Hashomer, Israel
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Gynaecological Cancer Research Laboratories, UCL EGA Institute for Women's Health, University College London, London, UK
Department of Preventive Medicine, Keck School of Medicine University of Southern California, Los Angeles, USA
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
Cancer Research United Kingdom Department of Oncology and Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK


© Bolton et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.