Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2015 Feb 1;21(3):652-7. doi: 10.1158/1078-0432.CCR-14-2497. Epub 2014 Nov 14.

Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.

Author information

  • 1Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.
  • 2Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom.
  • 3Mayo Clinic, Rochester, Minnesota.
  • 4University of Kansas Medical Center, Kansas City, Kansas.
  • 5The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • 6Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
  • 7Department of Gynaecological Oncology, Crown Princess Mary Cancer Centre and Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Sydney NSW, Australia.
  • 8Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
  • 9University of Edinburgh Cancer Research UK Centre, MRC IGMM, Edinburgh, United Kingdom.
  • 10Ninewells Hospital and Medical School, Dundee, United Kingdom.
  • 11Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • 12Departments of Cancer Epidemiology and Oncology, Lund University, Lund, Sweden.
  • 13Royal Marsden NHS Foundation Trust, London, United Kingdom.
  • 14Human Genetics Group and Human Genotyping Unit Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
  • 15Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital; Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
  • 16Laboratory Medicine Program, University Health Network; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
  • 17Hereditary Cancer Program, Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain.
  • 18Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California.
  • 19Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy.
  • 20Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
  • 21The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong, Hong Kong.
  • 22Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • 23Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
  • 24Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California.
  • 25University of California San Francisco, Cancer Risk Program, San Francisco, California.
  • 26Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
  • 27Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
  • 28Departments of Internal Medicine and Molecular Virology, Immunology, and Medical Genetics, The Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
  • 29VIB Vesalius Research Center, University of Leuven, Leuven, Belgium.
  • 30Departments of Oncology and Radiology, Cambridge University Hospitals Foundation Trust, Cambridge, United Kingdom. CR-UK Cambridge Institute, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom. Cambridge Experimental Cancer Medicine Centre, Cambridge, United Kingdom.
  • 31Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
  • 32QIMR Berghofer Medical Research Institute, Herston, Australia.
  • 33Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom. paul.pharoah@srl.cam.ac.uk.

Abstract

PURPOSE:

To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.

EXPERIMENTAL DESIGN:

We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.

RESULTS:

The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.

CONCLUSIONS:

BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.

©2014 American Association for Cancer Research.

PMID:
25398451
[PubMed - indexed for MEDLINE]
PMCID:
PMC4338615
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk