Purpose: Mammographic breast density (BD) is associated with increased risk of breast cancer. This study asks which circulating metabolic and reproductive biomarkers are associated with BD, particularly dense breast area, in premenopausal women not taking exogenous hormones.
Methods: In a cross-sectional study, 299 premenopausal women aged 40-49 completed questionnaires, provided a fasting blood sample, had height, weight, percentage body fat, waist and hip measurements taken, and attended a screening mammogram. Multivariate linear regression was used to calculate adjusted means for percentage BD, absolute dense and non-dense area, across categories of covariates, adjusted for day of menstrual cycle, age, parity, body mass index, percentage body fat, and ethnicity.
Results: Fasting insulin levels were inversely associated, and insulin-like growth factor-binding protein 1 levels directly associated with percentage BD, but lost statistical significance after multivariate adjustment. Sex hormone-binding globulin levels were directly associated with percentage BD, still significant after multivariate adjustment (p = 0.03). A significant inverse dose-response association was observed between progesterone levels and dense area (p < 0.01).
Conclusions: Breast density in premenopausal women seems unrelated or inversely related to insulin resistance, levels of insulin-like growth factor 1 and its binding proteins, and levels of sex steroids; therefore, the mechanism by which radiodensity on a mammogram is related to breast cancer risk remains unclear.