Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.
BACKGROUND
Studies of survival following breast and ovarian cancers in BRCA1 and/or BRCA2 mutation carriers have yielded conflicting results. We undertook an analysis of a community-based study of Ashkenazi Jews to investigate the effect of three founder mutations in BRCA1 and BRCA2 on survival among patients with breast or ovarian cancer.


METHODS
We collected blood samples and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (single nucleotide insertion) mutations in BRCA1 and the 6174delT (single nucleotide deletion) mutation in BRCA2. To estimate survival differences in the 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 relatives had been diagnosed with breast cancer and 10 with ovarian cancer; 907 noncarriers reported 979 first-degree relatives with breast cancer and 116 with ovarian cancer. Kaplan-Meier estimates of median survival after breast cancer were 16 years (95% confidence interval [CI] = 11-40) in the relatives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarriers, a difference that was not statistically significant (two-sided P = .87). There was also no difference in survival times among the 126 first-degree relatives with ovarian cancer. We found no survival difference between patients with breast or ovarian cancer who were inferred carriers of BRCA1 and/or BRCA2 mutations and noncarriers.


CONCLUSIONS
Carriers of BRCA1 and BRCA2 mutations appeared to have neither better nor worse survival prognosis.
Howard Hughes Medical Institute, Bethesda, MD, USA.
J S
JS
Lee
S
S
Wacholder
J P
JP
Struewing
M
M
McAdams
D
D
Pee
L C
LC
Brody
M A
MA
Tucker
P
P
Hartge
D000328:Adult; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000401:mortality*; D004219:District of Columbia / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000706:statistics & numerical data*; D016014:Linear Models; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D015996:Survival Rate