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

Lesley M. Butler, Ellen B. Gold, Gail A. Greendale, Carolyn J. Crandall, Francesmary Modugno, Nina Oestreicher, Charles P. Quesenberry, Laurel A. Habel

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 <or=23 years versus no births), greater number of births (beta=-6.80, P<0.01 for >or=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 >or=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.