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 in 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.
Hartge
Patricia
P
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7246, USA. hartgep@exchange.nih.gov
Chatterjee
Nilanjan
N
Wacholder
Sholom
S
Brody
Lawrence C
LC
Tucker
Margaret A
MA
Struewing
Jeffery P
JP
D000328:Adult; D000367:Age Factors; D001722:Birth Order; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics; D015331:Cohort Studies; D004219:District of Columbia / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D009154:Mutation; D010298:Parity / Q000235:genetics; D012307:Risk Factors