Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors.

We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors, including body mass index (BMI), age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. This study included 1,044 postmenopausal incident breast cancer cases diagnosed within the Nurses' Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense, and non-dense areas were measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Percent breast density was more strongly associated with breast cancer risk in current postmenopausal hormone users (≥50 vs. 10 %: OR 5.34, 95 % CI 3.36-8.49) as compared to women with past (OR 2.69, 95 % CI 1.32-5.49) or no hormone history (OR 2.57, 95 % CI 1.18-5.60, p-interaction = 0.03). Non-dense area was inversely associated with breast cancer risk in parous women, but not in women without children (p-interaction = 0.03). Associations of density with breast cancer risk did not differ by the levels of BMI, age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. Women with dense breasts, who currently use menopausal hormone therapy are at a particularly high risk of breast cancer. Most breast cancer risk factors do not modify the association between mammographic breast density and breast cancer risk.