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

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 and Ramus, Susan J, et al. (2015) In Clinical Cancer Research 21(3). p.7-652
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EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies.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... (More)

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EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies.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.

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Aged, Female, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, Humans, Middle Aged, Neoplasm Grading, Neoplasm Staging, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Prognosis, Survival Analysis, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
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Clinical Cancer Research
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21
issue
3
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6 pages
publisher
American Association for Cancer Research
external identifiers
  • pmid:25398451
  • wos:000348908500020
  • scopus:84961291899
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-14-2497http://dx.doi.org/10.1158/1078-0432.CCR-14-2497
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English
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yes
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8078080a-4b99-4821-86e6-524080ddf2fd (old id 4816564)
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http://www.ncbi.nlm.nih.gov/pubmed/25398451?dopt=Abstract
date added to LUP
2014-12-02 17:50:45
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2017-11-12 03:09:22
@article{8078080a-4b99-4821-86e6-524080ddf2fd,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.</p>},
  author       = {Candido-dos-Reis, Francisco J and Song, Honglin and Goode, Ellen L and Cunningham, Julie M and Fridley, Brooke L and Larson, Melissa C and Alsop, Kathryn and Dicks, Ed and Harrington, Patricia and Ramus, Susan J and de Fazio, Anna and Mitchell, Gillian and Fereday, Sian and Bolton, Kelly L and Gourley, Charlie and Michie, Caroline and Karlan, Beth and Lester, Jenny and Walsh, Christine and Cass, Ilana and Olsson, Håkan and Gore, Martin and Benitez, Javier J and Garcia, Maria J and Andrulis, Irene and Mulligan, Anna Marie and Glendon, Gord and Blanco, Ignacio and Lazaro, Conxi and Whittemore, Alice S and McGuire, Valerie and Sieh, Weiva and Montagna, Marco and Alducci, Elisa and Sadetzki, Siegal and Chetrit, Angela and Kwong, Ava and Kjaer, Susanne K and Jensen, Allan and Høgdall, Estrid and Neuhausen, Susan and Nussbaum, Robert and Daly, Mary and Greene, Mark H and Mai, Phuong L and Loud, Jennifer T and Moysich, Kirsten and Toland, Amanda E and Lambrechts, Diether and Ellis, Steve and Frost, Debra and Brenton, James D and Tischkowitz, Marc and Easton, Douglas F and Antoniou, Antonis and Chenevix-Trench, Georgia and Gayther, Simon A and Bowtell, David and Pharoah, Paul D P and , },
  issn         = {1078-0432},
  keyword      = {Aged,Female,Genes, BRCA1,Genes, BRCA2,Germ-Line Mutation,Humans,Middle Aged,Neoplasm Grading,Neoplasm Staging,Neoplasms, Glandular and Epithelial,Ovarian Neoplasms,Prognosis,Survival Analysis,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, Non-P.H.S.},
  language     = {eng},
  month        = {02},
  number       = {3},
  pages        = {7--652},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-14-2497http://dx.doi.org/10.1158/1078-0432.CCR-14-2497},
  volume       = {21},
  year         = {2015},
}