BACKGROUND: Breast cancer survivors (BCS) face a higher risk of cardiovascular disease (CVD) due to treatment-related cardiotoxicity and pre-existing conditions. We investigated how post-diagnosis weight changes and obesity impact CVD risk in this population. METHOD: Using the Korean National Health Insurance Service database (2010-2019), BCS without previous history of CVD were enrolled. Weight change was determined using standardized anthropometric protocols during biennial health examinations pre- and post-diagnosis. The primary outcome was incident CVD, a composite of myocardial infarction (MI) and ischemic stroke. Adjusted hazard ratios (aHRs) and confidence intervals (CIs) were estimated, accounting for cardiovascular risk factors, cancer treatments, and sociodemographic variables. RESULTS: During a mean follow-up of 3.70 years among the 42,547 BCS (mean [SD] age 53.4 [9.4] years), substantial weight gain (>
10%) was associated with increased CVD risk (aHR 1.66, 95% CI 1.05-2.62) and MI risk (aHR 1.83, 95% CI 1.01-3.33) compared to those who maintained their weight. The association between change in obesity status and CVD risk was not significant. Among BCS with sustained obesity, CVD risk was more pronounced in younger survivors (<
50 years) (aHR 3.58, 95% CI 1.94-6.61), and in those using tamoxifen (aHR 1.74, 95% CI 1.11-2.75) (P-interactions <
0.05). CONCLUSIONS: Our findings suggest that BCS who experience substantial weight gain post-diagnosis have an increased risk of CVD. Further intervention studies (e.g., GLP-1 agonist) are needed to ascertain the effects of weight changes on CVD risks in BCS.