Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer

Kelly L. Bolton, Georgia Chenevix-Trench, Cindy Goh, Siegal Sadetzki, Susan J. Ramus, Beth Y. Karlan, Diether Lambrechts, Evelyn Despierre, Daniel Barrowdale, Lesley McGuffog, Sue Healey, Douglas F. Easton, Olga Sinilnikova, Javier Benítez, María J. García, Susan Neuhausen, Mitchell H. Gail, Patricia Hartge, Susan Peock, Debra FrostD. Gareth Evans, Rosalind Eeles, Andrew K. Godwin, Mary B. Daly, Ava Kwong, Edmond S.K. Ma, Conxi Lázaro, Ignacio Blanco, Marco Montagna, Emma D'Andrea, Maria Ornella Nicoletto, Sharon E. Johnatty, Susanne Krüger Kjær, Allan Jensen, Estrid Høgdall, Ellen L. Goode, Brooke L. Fridley, Jennifer T. Loud, Mark H. Greene, Phuong L. Mai, Angela Chetrit, Flora Lubin, Galit Hirsh-Yechezkel, Gord Glendon, Irene L. Andrulis, Amanda E. Toland, Leigha Senter, Martin E. Gore, Charlie Gourley, Caroline O. Michie, Honglin Song, Jonathan Tyrer, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Ulf Kristoffersson, Håkan Olsson, Åke Borg, Douglas A. Levine, Linda Steele, Mary S. Beattie, Salina Chan, Robert L. Nussbaum, Kirsten B. Moysich, Jenny Gross, Ilana Cass, Christine Walsh, Andrew J. Li, Ronald Leuchter, Ora Gordon, Montserrat Garcia-Closas, Simon A. Gayther, Stephen J. Chanock, Antonis C. Antoniou, Paul D.P. Pharoah

Research output: Contribution to journalArticle

357 Scopus citations

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 amore 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.

Original languageEnglish (US)
Pages (from-to)382-390
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number4
DOIs
StatePublished - Jan 25 2012

ASJC Scopus subject areas

  • Medicine(all)

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    Bolton, K. L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S. J., Karlan, B. Y., Lambrechts, D., Despierre, E., Barrowdale, D., McGuffog, L., Healey, S., Easton, D. F., Sinilnikova, O., Benítez, J., García, M. J., Neuhausen, S., Gail, M. H., Hartge, P., Peock, S., ... Pharoah, P. D. P. (2012). Association between BRCA1 and BRCA2 Mutations and Survival in Women with Invasive Epithelial Ovarian Cancer. JAMA - Journal of the American Medical Association, 307(4), 382-390. https://doi.org/10.1001/jama.2012.20