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Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer

Bolton, Kelly L.; Chenevix-Trench, Georgia; Goh, Cindy; Sadetzki, Siegal; Ramus, Susan J.; Karlan, Beth Y.; Lambrechts, Diether; Despierre, Evelyn; Barrowdale, Daniel and McGuffog, Lesley, et al. (2012) In JAMA: the journal of the American Medical Association 307(4). p.382-390
Abstract
Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times... (More)
Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390 (Less)
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JAMA: the journal of the American Medical Association
volume
307
issue
4
pages
382 - 390
publisher
American Medical Association
external identifiers
  • wos:000299464000024
  • scopus:84856158117
ISSN
1538-3598
DOI
10.1001/jama.2012.20
language
English
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yes
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63c9393a-89ed-4178-8180-7aabcf107793 (old id 2348868)
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2012-03-01 11:24:52
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2017-11-05 04:03:54
@article{63c9393a-89ed-4178-8180-7aabcf107793,
  abstract     = {Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P&lt;.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P&lt;.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P&lt;.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P&lt;.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390},
  author       = {Bolton, Kelly L. and Chenevix-Trench, Georgia and Goh, Cindy and Sadetzki, Siegal and Ramus, Susan J. and Karlan, Beth Y. and Lambrechts, Diether and Despierre, Evelyn and Barrowdale, Daniel and McGuffog, Lesley and Healey, Sue and Easton, Douglas F. and Sinilnikova, Olga and Benitez, Javier and Garcia, Maria J. and Neuhausen, Susan and Gail, Mitchell H. and Hartge, Patricia and Peock, Susan and Frost, Debra and Evans, Gareth and Eeles, Rosalind and Godwin, Andrew K. and Daly, Mary B. and Kwong, Ava and Ma, Edmond S. K. and Lazaro, Conxi and Blanco, Ignacio and Montagna, Marco and D'Andrea, Emma and Nicoletto, Maria Ornella and Johnatty, Sharon E. and Krueger, Susanne and Jensen, Allan and Hogdall, Estrid and Goode, Ellen L. and Fridley, Brooke L. and Loud, Jennifer T. and Greene, Mark H. and Mai, Phuong L. and Chetrit, Angela and Lubin, Flora and Hirsh-Yechezkel, Galit and Glendon, Gord and Andrulis, Irene L. and Toland, Amanda E. and Senter, Leigha and Gore, Martin E. and Gourley, Charlie and Michie, Caroline O. and Song, Honglin and Tyrer, Jonathan and Whittemore, Alice S. and McGuire, Valerie and Sieh, Weiva and Kristoffersson, Ulf and Olsson, Håkan and Borg, Åke and Levine, Douglas A. and Steele, Linda and Beattie, Mary S. and Chan, Salina and Nussbaum, Robert L. and Moysich, Kirsten B. and Gross, Jenny and Cass, Ilana and Walsh, Christine and Li, Andrew J. and Leuchter, Ronald and Gordon, Ora and Garcia-Closas, Montserrat and Gayther, Simon A. and Chanock, Stephen J. and Antoniou, Antonis C. and Pharoah, Paul D. P.},
  issn         = {1538-3598},
  language     = {eng},
  number       = {4},
  pages        = {382--390},
  publisher    = {American Medical Association},
  series       = {JAMA: the journal of the American Medical Association},
  title        = {Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer},
  url          = {http://dx.doi.org/10.1001/jama.2012.20},
  volume       = {307},
  year         = {2012},
}