| Authors: |
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.; Frost, D.; Evans, D. G.; Eeles, R.; Godwin, A. K.; Daly, M. B.; Kwong, A.; Ma, E. S. K.; Lazaro, C.; Blanco, I.; Montagna, M.; D'Andrea, E.; Nicoletto, M. O.; Johnatty, S. E.; Kjær, S. K.; Jensen, A.; Høgdall, E.; Goode, E. L.; Fridley, B. L.; Loud, J. T.; Greene, M. H.; Mai, P. L.; Chetrit, A.; Lubin, F.; Hirsh-Yechezkel, G.; Glendon, G.; Andrulis, I. L.; Toland, A. E.; Senter, L.; Gore, M. E.; Gourley, C.; Michie, C. O.; Song, H.; Tyrer, J.; Whittemore, A. S.; McGuire, V.; Sieh, W.; Kristoffersson, U.; Olsson, H.; Borg, A.; Levine, D. A.; Steele, L.; Beattie, M. S.; Chan, S.; Nussbaum, R. L.; Moysich, K. B.; Gross, J.; Cass, I.; Walsh, C.; Li, A. J.; Leuchter, R.; Gordon, O.; Garcia-Closas, M.; Gayther, S. A.; Chanock, S. J.; Antoniou, A. C.; Pharoah, P. D. P. |
| 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. ©2012 American Medical Association. All rights reserved. |
