Mammographic breast density and breast cancer risk in a Mediterranean population: a nested case-control study in the EPIC Florence cohort

Mammographic breast density (MBD) has been consistently associated with breast cancer (BC) risk, and at the same time it is modulated by established BC risk factors related to reproductive and hormonal history and to lifestyle. We aimed to evaluate the association between the clinical breast imaging reporting and data system (BI-RADS), a qualitative MBD classification used in clinical setting, and BC risk through a case-control nested in the EPIC Florence cohort where baseline information on reproductive history, lifestyle and anthropometry were collected. The study includes 136 newly diagnosed BC cases and 635 controls from the 10,083 healthy women enroled in the cohort between 1993 and 1998 and followed for 6 years on average. MBD was assessed on a negative mammogram performed at least one year before diagnosis in cases and on a mammogram performed in the same period for controls matched for age, enrolment date and menopausal status. Multivariate analyses adjusted for education, body mass index, parity, number of children, breastfeeding, BC family history, history of breast biopsies and Hormone Replacement Therapy use were performed. An increase in BC risk across BI-RADS categories emerged with adjusted odds ratios (OR) 1.79 (95% CI 1.06-3.01), OR 2.09 (95% CI 1.17-3.74) and OR 2.67 (95% CI 1.08-6.62) for categories 2, 3 and 4 in comparison with the reference category (p for trend = 0.008). We confirm in this Mediterranean population the association of increasing MBD, classified according to BI-RADS with BC risk also taking into account other well-known risk factors for this neoplasm.