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. 2012 Jan 25;307(4):382-90.
doi: 10.1001/jama.2012.20.

Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

Kelly L Bolton  1 , 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 Frost, D 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; EMBRACE; kConFab Investigators; Cancer Genome Atlas Research Network
Collaborators, Affiliations

Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

Kelly L Bolton et al. JAMA. .

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 < .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.

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Figures

Figure 1
Figure 1. Kaplan Meier Estimates of Cumulative Survival According to BRCA1/2 status
Caption: Kaplan Meier analysis was adjusted for year of diagnosis and study.
See this image and copyright information in PMC

Comment in

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