Longitudinal study of birthweight and the incidence of breast cancer in adulthood.

A high birthweight has been associated with an increased risk of breast cancer later in life. The role of adult variables, possible effect modifiers and cancer characteristics has been little studied. We explored these in two large prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II). We collected information on birthweight from 152,608 female nurses participating in NHS and NHS II. During 10 years and 1.3 million person-years of follow-up, invasive breast cancer was newly diagnosed among 828 premenopausal and 2312 postmenopausal women. Data were analyzed using a Cox proportional hazards model. Premenopausal women with a birthweight of <5.5 lbs had a covariate-adjusted hazard ratio (HR) for breast cancer of 0.66 [95% confidence interval (CI) 0.47-0.93] compared with women born at 8.5 lbs or above. Adult height was the only factor explaining some of the association between birthweight and breast cancer incidence; after adjustment for height the HR was 0.73 (95% CI 0.51-1.03). The association between birthweight and the incidence of breast cancer was stronger among women with estrogen-receptor positive and progesterone-receptor positive breast cancer. Among postmenopausal women, no important association between the birthweight and the incidence of breast cancer was detected (HR comparing women with a birthweight of 5.5 lbs or less with women with a birthweight>8.5 lbs: 0.97; 95% CI 0.80-1.16). In these two large prospective cohorts, a low birthweight was associated with a decreased incidence of breast cancer among premenopausal women. This association was independent of other factors operating later in life, except for adult height.