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

Epidemiology. 2002 May;13(3):255-61. doi: 10.1097/00001648-200205000-00004.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Birth Order
  • Breast Neoplasms / ethnology*
  • Breast Neoplasms / genetics
  • Cohort Studies
  • District of Columbia / epidemiology
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Jews / genetics*
  • Male
  • Mutation
  • Parity* / genetics
  • Risk Factors