Menstrual and reproductive factors in relation to mammographic density: the Study of Women's Health Across the Nation (SWAN)

Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (beta = 10.3, P < 0.01, for > 13 vs. < 12 years), premenstrual cravings and bloating (beta = -3.36, P = 0.02), younger age at first full-term birth (beta = -8.12, P < 0.01 for <= 23 years versus no births), greater number of births (beta = -6.80, P < 0.01 for >= 3 births versus no births), and premenopausal status (beta = 3.78, P < 0.01 versus early perimenopausal). Only number of births remained associated with percent density after adjustment for age, race/ethnicity, study site, body mass index (BMI), and smoking. In addition, stratified analyses revealed that the association with number of births was confined to women within the lowest BMI tertile (beta = -12.2, P < 0.01 for >= 3 births versus no births). Our data support a mechanism for parity and breast cancer that involves mammographic density among pre- and early perimenopausal women that may be modified by body size.