Tobacco smoke has both carcinogenic effects and anti-estrogenic properties and its inconsistent association with breast cancer risk in observational studies may be because of these competing effects across the lifecourse. We conducted a prospective study of prenatal smoke exposure, childhood household smoke exposure, and adult active smoke exposure and mammographic density, a strong intermediate marker of breast cancer risk, in an adult follow-up of existing US birth cohorts. Specifically, we followed up women who were born between 1959 and 1967 and whose mothers participated in either the Collaborative Perinatal Project (Boston and Providence sites) or the Childhood Health and Development Study in California. Of the 1134 women interviewed in adulthood (ranging in age from 39 to 49 years at interview), 79% had a screening mammogram. Cigarette smoking was reported by mothers at the time of their pregnancy; 40% of mothers smoked while pregnant. Women whose mothers smoked during pregnancy had a 3.1% (95% confidence interval (CI) = −6.0%, −0.2%) lower mammographic density than women whose mothers did not smoke during pregnancy. When we further accounted for adult body mass index and adult smoking status, the association remained (β = −2.7, 95% CI = −5.0, −0.3). When we examined patterns of smoking, prenatal smoke exposure without adult smoke exposure was associated with a 5.6% decrease in mammographic density (β = −5.6, 95% CI = −9.6, −1.6). Given the strength of mammographic density as an intermediate marker for breast cancer, the inverse associations between mammographic density and smoking patterns across the lifecourse may help explain the complex association between cigarette smoking and breast cancer risk.
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