Body mass index, mammographic density and post-menopausal breast cancer risk: a mediation analysis v1

Le résumé fourni par la source

Background: Body mass index (BMI) and mammographic density (MD) are established but inversely correlated determinants of breast cancer risk. While higher BMI in post-menopausal women increases risk, greater BMI in early adulthood appears protective. MD, reflecting the proportion of fibroglandular to fatty tissue, is a strong positive risk factor. The extent to which MD mediates the protective association of early-adult BMI with post-menopausal breast cancer remains unclear. Methods: We will perform a mediation analysis within the Predicting Risk of Cancer at Screening (PROCAS) cohort (>57,000 women, UK NHS Breast Screening Programme). Early-adult BMI (age 18–21 years) is self-reported at recruitment; MD is measured at screening using visual analogue scales (VAS) and automated volumetric methods. Post-menopausal breast cancer incidence is determined through national cancer registry linkage. Analyses will estimate natural direct and indirect effects of early-adult BMI on cancer risk mediated by MD, using counterfactual mediation models with bootstrap confidence intervals, guided by an investigator-derived directed acyclic graph. Expected Impact: This study will clarify causal pathways linking adiposity and breast tissue composition to post-menopausal breast cancer. Findings may refine mechanistic understanding, improve individualised risk prediction, and support life-course strategies for breast cancer prevention. Keywords: Body mass index, mammographic density, breast cancer, mediation analysis, PROCAS

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