Title: Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
Authors: Candido Dos Reis, Francisco J ×
Song, Honglin
Goode, Ellen L
Cunningham, Julie M
Fridley, Brooke L
Larson, Melissa C
Alsop, Kathryn
Dicks, Ed
Harrington, Patricia
Ramus, Susan J
de Fazio, Anna
Mitchell, Gillian
Fereday, Sian
Bolton, Kelly L
Gourley, Charlie
Michie, Caroline
Karlan, Beth Y
Lester, Jenny
Walsh, Christine
Cass, Ilana
Olsson, Hakan
Gore, Martin
Benitez, Javier
Garcia, Maria J
Andrulis, Irene L
Mulligan, Anna Marie
Glendon, Gord
Blanco, Ignacio
Lazaro, Conxi
Whittemore, Alice S
McGuire, Valerie
Sieh, Weiva
Montagna, Marco
Alducci, Elisa
Sadetzki, Siegal
Chetrit, Angela
Kwong, Ava
Kjaer, Susanne K
Jensen, Allan
Høgdall, Estrid
Neuhausen, Susan L
Nussbaum, Robert L
Daly, Mary
Greene, Mark H
Mai, Phuong L
Loud, Jennifer T
Moysich, Kirsten B
Toland, Amanda Ewart
Lambrechts, Diether
Ellis, Steve
Frost, Debra
Brenton, James D
Tischkowitz, Marc
Easton, Douglas F
Antoniou, Antonis C
Chenevix-Trench, Georgia
Gayther, Simon A
Bowtell, David D L
Pharoah, Paul D P #
Issue Date: Feb-2015
Publisher: Association for Cancer Research
Series Title: Clinical Cancer Research vol:21 issue:3 pages:652-7
Article number: clincanres.2497.2014
Abstract: Purpose:To analyse the effect of germline mutations in BRCA1 and BRCA2 on mortality in ovarian cancer patients up to ten 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 Experimental Design:We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival-time data for 4,314 patients from previously reported studies.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 analysed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analysed using Fine and Gray model. Results: The combined 10-year overall survival was 30% (95% CI, 28%-31%) for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The hazard ratio for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the hazard ratio was 0.42 at time zero and increased over time (predicted to become greater than one 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.
ISSN: 1078-0432
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (VIB-KU Leuven Center for Cancer Biology)
× corresponding author
# (joint) last author

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