The FEDRA Longitudinal Study: Repeated Volumetric Breast Density Measures and Breast Cancer Risk

SIMPLE SUMMARY: Mammographic breast density is a strong independent risk factor for breast cancer. We investigated the association between volumetric mammographic breast density measures, their changes over time, and breast cancer risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. For the 6148 study women (262 breast cancer cases, average 7.8 years of follow-up), repeated measures of mammographic breast density from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry were available. The association between mammographic breast density measures (modeled as time-dependent covariates), their relative annual changes, and breast cancer risk was evaluated by adjusted Cox models. Higher values of volumetric percent density and dense volume were positively associated with increased breast cancer risk, while an inverse association was evident for increasing non-dense volume. No clear effect of annual changes in mammographic breast density emerged. ABSTRACT: Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We investigated the association between volumetric MBD measures, their changes over time, and BC risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. The study was carried out among 6148 women with repeated MBD measures from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry. The association between MBD measures (modeled as time-dependent covariates), their relative annual changes, and BC risk were evaluated by adjusted Cox models. During an average of 7.8 years of follow-up, 262 BC cases were identified. BC risk was directly associated with standard deviation increments of volumetric percent density (VPD, HR 1.37, 95%CI 1.22–1.54) and dense volume (DV, HR 1.29, 95%CI 1.18–1.41). An inverse association emerged with non-dense volume (NDV, HR 0.82, 95%CI 0.69–0.98). No significant associations emerged between annual changes in VPD, DV, NDV, and BC risk. Higher values of MBD measures, modeled as time-dependent covariates, were positively associated with increased BC risk, while an inverse association was evident for increasing NDV. No effect of annual changes in MBD emerged.