Mammographic breast density and breast cancer risk by menopausal status, postmenopausal hormone use and a family history of breast cancer

Purpose: Few studies have investigated the association between breast density and breast cancer by a family history of breast cancer, menopausal status, and postmenopausal hormone use (PMH). We investigated if associations of breast density and breast cancer differ according to the status of these risk factors. Methods: This study included 1,481 incident breast cancer cases diagnosed within the Nurses' Health Study I and II cohorts and 2,779 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of the cancer diagnosis for cancer cases and their matched controls. The data were analyzed with logistic regression. Results: Breast cancer risk increased with increasing percent breast density in all strata (p for trend in all subsets <0.0001). The density-related risk of breast cancer was similar in women with and without a family history (OR = 4.00 [95% CI 2.01-7.94] vs. 3.71 [95% CI 2.79-4.94] for density ≥50% vs. <10%, p for interaction = 0.53). The magnitude of the association between density and breast cancer risk, however, appeared to be stronger in premenopausal women than in postmenopausal women without PMH history (OR = 5.49 [95% CI 2.44-12.39] vs. 3.02 [95% CI 1.62-5.63] for density ≥50%vs.≥10%, p-heterogeneity = 0.17) and appeared to be stronger in postmenopausal women currently using hormones compared with postmenopausal women who never used PMH (OR = 4.50 [95% CI 2.99-6.78] vs. 3.02, p-heterogeneity = 0.20) or with past hormone use (OR = 4.50 vs. 3.71 [95%CI 1.90-7.23], p-heterogeneity = 0.23). Conclusions: Findings on associations by menopausal status/hormone use are suggestive and should be examined in additional larger studies.