Format

Send to

Choose Destination
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

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

PMID:
25398451
PMCID:
PMC4338615
DOI:
10.1158/1078-0432.CCR-14-2497
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Supplementary concept, Grant support

Publication types

MeSH terms

Supplementary concept

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center