1001 - Baseline Cardiovascular Comorbidity, Tumor Laterality, and Major Adverse Cardiovascular Events After Breast Radiotherapy: A Multi-Institutional EHR Cohort Study

Purpose/Objective(s): Cardiovascular disease is a leading cause of non-cancer mortality after breast radiotherapy (RT), yet the relative contributions of baseline cardiovascular (CV) risk versus treatment-related factors remain poorly characterized. We sought to determine whether pre-existing CV comorbidity, indicated by cardioprotective medication use (ACE inhibitors/ARBs, statins, or metformin) is associated with 5-year major adverse cardiovascular events (MACE) more strongly than tumor laterality in a large real-world breast RT cohort.

Materials/Methods: We conducted a retrospective cohort study using a multi-institutional EHR-derived dataset (Epic Cosmos) of breast cancer patients diagnosed on or after 1/1/2015 with known tumor laterality who received RT. Patients were stratified by laterality and cardioprotective medication exposure during RT into four groups: left-with-drug, left-without-drug, right-with-drug, right-without-drug. The primary endpoint was time to MACE. Kaplan–Meier estimates and multivariable Cox models were fit adjusting for age, Social Vulnerability Index, Charlson Comorbidity Index, race, insurance, region, and TNM stage.

Results: Among 55,711 patients (left-with-drug n=8,502; left-without-drug n=19,847; right-with-drug n=8,190; right-without-drug n=19,172), 4,953 MACE events occurred. Five-year MACE-free survival was markedly lower in medication-exposed groups regardless of laterality (left-with-drug 0.861, right-with-drug 0.863) compared to unexposed groups (left-without-drug 0.938, right-without-drug 0.936). Using left-with-drug as reference, adjusted hazards were lower for left-without-drug (HR 0.69, 95% CI 0.64–0.75, p<0.001) and right-without-drug (HR 0.70, 95% CI 0.64–0.75, p<0.001), while right-with-drug showed no difference (HR 1.01, 95% CI 0.93–1.09, p=0.8). In an ACEi/ARB subgroup analysis for rhythmic disorders, the same pattern held: event-free survival stratified by medication status (with-ACEi/ARB ~0.79 vs. without ~0.87) rather than laterality.

Conclusion: In this large multi-institutional cohort, baseline CV comorbidity as reflected by cardioprotective medication use was associated with 5-year MACE after breast RT, while laterality-specific differences were minimal after adjustment. These findings suggest that optimizing modifiable CV risk factors before and during RT may be more impactful than laterality-based risk stratification alone. Given the inherent confounding by indication, prospective studies incorporating causal inference methods and detailed cardiac dosimetric data are needed to determine whether cardioprotective pharmacotherapy independently modifies radiation therapy–related cardiac risk.