Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

Background: Studies of survival following breast and ovarian cancers in BRC A1 and/or BRCA2 mutation carriers have yielded conflicting results. We unde rtook an analysis of a community-based study of Ashkenazi Jews to investiga te the effect of three founder mutations in BRCA1 and BRCA2 on survival amo ng patients with breast or ovarian cancer. Methods: We collected blood samp les and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (s ingle nucleotide insertion) mutations in BRCA1 and the 6174delT (single nuc leotide deletion) mutation in BRCA2. To estimate survival differences in th e affected relatives according to their BRCA1 and/or BRCA2 mutation carrier status, we devised and applied a novel extension of the kin-cohort method. Results: Fifty mutation carriers reported that 58 of their first-degree re latives had been diagnosed with breast cancer and 10 with ovarian cancer; 9 07 noncarriers reported 979 first-degree relatives with breast cancer and 1 16 with ovarian cancer. Kaplan-Meier estimates of median survival after bre ast cancer were 16 years (95% confidence interval [CI] = 11-40) in the rela tives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarr iers, a difference that was not statistically significant (two-sided P = .8 7). There was also no difference in survival times among the 126 first-degr ee relatives with ovarian cancer. We found no survival difference between p atients with breast or ovarian cancer who were inferred carriers of BRCA1 a nd/or BRCA2 mutations and noncarriers. Conclusions: Carriers of BRCA1 and B RCA2 mutations appeared to have neither better nor worse survival prognosis .