Breast cancer risk in Ashkenazi BRCA1/2 mutation carriers: Effects of reproductive history

Background. Younger age at first birth and greater parity generally reduce the risk of developing breast cancer, but whether this reduced risk holds in women with a mutation in the BRCA1 or BRCA2 gene is unknown. Methods. In a Washington DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an extension of the "kin-cohort" analysis, we compared the effects of reproduction on breast cancer risk in carriers and noncarriers. We also used a case-case analysis among 288 participants who had been diagnosed with breast cancer. Results. In noncarriers, the estimated relative risk (RR) of breast cancer rose 5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers fell with each 5-year increment tn age (RR = 0.65; 95% CI = 0.37-1.16). Among the 288 participants who were breast cancer survivors themselves, the comparison of carriers with noncarriers also showed no protection associated with early birth in the presence of a mutation in BRCA1 or BRCA2. Conclusions. It is not yet clear whether the recognized breast cancer risk factors operate in the same way in women who carry a mutation in the BRCA1 or BRCA2 genes.