Early-adulthood body mass index, mammographic density and post-menopausal breast cancer risk: a mediation analysis
Menée à partir de données de la cohorte "UK PROCAS" portant sur 33 816 femmes ménopausées (durée médiane de suivi : 10,44 ans), cette étude analyse le rôle de la densité mammaire dans l'association entre l'indice de masse corporelle à 20 ans et le risque de cancer du sein après la ménopause
Background: To explore potential mechanistic pathways and inform prevention strategies, this study examined whether mammographic density (MD) mediates the inverse association between higher early-adulthood body mass index (BMI) and lower post-menopausal breast cancer risk.
Methods: We analysed data from 33,816 post-menopausal women in the UK PROCAS cohort, with self-reported BMI at age 20. MD was measured using full-field digital mammography and assessed using the visual analogue scale (VAS) percentage density and Volpara®-derived fibroglandular volume (FGV). Counterfactual mediation modelling estimated natural direct and indirect effects.
Results: Over a median follow-up of 10.44 years, there were 1261 new post-menopausal breast cancers. Higher VAS and FGV were associated with increased breast cancer risk. BMI at age 20 was associated with lower VAS density and reduced breast cancer risk [Hazard Ratio per 5 kg/m²: 0.849 (0.771–0.938)]. The calculated proportion mediated by VAS density was 59.9% (32.6–150), after accounting for intermediate confounding by BMI in later adulthood. FGV was positively associated with higher BMI at cohort entry but not at age 20.
Conclusions: Lower VAS density may partially explain the inverse association between early-adulthood BMI and post-menopausal breast cancer risk. The link between FGV and breast cancer risk may represent a different biological pathway.
British Journal of Cancer , article en libre accès, 2026