Abstract Background: Obesity is a known risk factor for breast cancer; however, its biological pathways remain to be fully understood. Lipid metabolism may play a role, yet its contribution has not been clearly quantified in large-scale population studies. Methods: We analyzed data from 2,088,751 postmenopausal Korean women who underwent national health screenings between 2009 and 2010, with follow-up through 2021. General and central adiposity were assessed using body mass index (BMI) and waist circumference (WC). Lipid biomarkers, including total cholesterol, HDL, LDL, and triglycerides, were measured during follow-up. Breast cancer incidence was identified via ICD-10 and catastrophic illness codes. Adjusted hazard ratios (HRs) were estimated using Cox regression, and causal mediation was examined using two-way and four-way decomposition methods. Results: During follow-up, 18,364 breast cancer cases were diagnosed. Compared with BMI 23.0 kg/m², HR was 1.84 (95% CI: 1.72-1.97) for BMI ≥ 30.0 kg/m². Compared with WC 80.0 cm, those with WC ≥ 88.0 cm, HR was 1.45 (95% confidence interval CI: 1.39-1.51). Mediation analyses showed that HDL and LDL cholesterol contributed modestly (5.5%), and most of the association was explained by direct effects. Conclusions: This study confirmed that obesity, particularly central adiposity, is a strong independent risk factor for postmenopausal breast cancer, with minimal mediation by lipid biomarkers. Impact: This large-scale cohort study underscores obesity as a key target for breast cancer prevention, independent of lipid profile status.
Nguyen et al. (2026) studied this question.