Association of METS-IR with breast cancer risk: a large-scale retrospective cohort study of Korean women

BACKGROUND: Insulin resistance has been linked to increased breast cancer risk through mechanisms involving metabolic dysfunction and chronic inflammation. This study aimed to investigate the association between the metabolic score for insulin resistance (METS-IR) and breast cancer incidence in a large cohort of Korean women. METHODS: We conducted a retrospective cohort analysis using data from 2,731,416 women aged ≥ 40 years, obtained from the 2009-2010 Korean National Health Screening Program. Participants had no prior history of breast cancer at baseline. METS-IR scores were calculated and stratified into quartiles. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence according to METS-IR quartiles. RESULTS: During 31,633,123 person-years of follow-up, 43,526 new breast cancer cases were identified. Women in the highest METS-IR quartile demonstrated a significantly increased breast cancer risk (HR: 1.07, 95% CI: 1.03-1.12) compared to those in the lowest quartile. This relationship exhibited a non-linear association, with the increased risk of breast cancer primarily driven by the highest quartile of metabolic dysfunction. CONCLUSIONS: Our findings validate METS-IR as a useful tool for breast cancer risk assessment among Korean women, highlighting the importance of insulin resistance as a modifiable metabolic risk factor. These results emphasize the need for targeted preventive interventions focusing on metabolic health to reduce breast cancer incidence.