Family history of breast cancer and short-term effects of childbirths on breast cancer risk

The long-term protective effect of a pregnancy on breast cancer risk is preceded by a short-term adverse effect, possibly reflecting a promoting effect of pregnancy hormones. In the present study, we explore whether a family history of breast cancer modifies time-related effects of pregnancies, with special emphasis on the transient increase in risk of breast cancer shortly after birth. Our study cohort comprises 1,067,289 Norwegian women aged 20-74 years. The mean follow-up time was 18 years. Incidence rate ratios were estimated by Poisson regression analyses of person-years at risk. Of the 7,377 women diagnosed with breast cancer during followup, a total of 828 (11%) had a mother or a sister with breast cancer diagnosis. Women with a family history of breast cancer had a 2-3-fold higher risk of breast cancer than did women without any affected family member, highest for those with a relative diagnosed before they were 50 years. Similar to women without a familial excess risk, increasing parity was associated with an overall protective effect among women with a familial predisposition, regardless of age at diagnosis of the relative. Whereas women with no familial excess risk experienced a transient increase in risk mainly after late age births, women with a family history of breast cancer experienced an adverse effect of pregnancies also at younger ages. The present results give further support to the hypothesis that the adverse effect of a term birth can be explained by a promoting effect of pregnancy hormones. (c) 2006 Wiley-Liss, Inc.