Interactions Between Mammographic Density Phenotypes and Established Risk Factors on Breast Cancer Risk, by Tumor Subtype and Menopausal Status.

Previous studies suggest that the association between mammographic density (MD) and breast cancer risk may be modified by other breast cancer risk factors. In this study, we assessed multiplicative interactions between MD measures and established risk factors on the risk of invasive breast cancer overall and by menopausal and estrogen receptor (ER) status. We used data on 2,137 cases and 4,346 controls from a nested case-control study within the Nurses' Health Studies I (1976-2004) and II (1989-2007), for whose data on percent mammographic density (PMD), absolute area of dense tissue (DA) and non-dense tissue (NDA) were available. No interaction remained statistically significant after adjusting for number of comparisons. For breast cancer overall, we observed nominally significant interactions (P < 0.05) between nulliparity and PMD/NDA, age at menarche and DA, and body mass index (BMI) and NDA. Individual nominally significant interactions across MD measures and risk factors were also observed in analyses stratified by either menopausal or ER status. Our findings help provide further insights into potential mechanisms underlying the association between MD and breast cancer.