Long-Term Risk of Cardiovascular Disease After Contemporary Left-Sided Breast Radiation Therapy

Importance: External beam radiation therapy (EBRT) for left-sided breast cancer historically increased the risk of cardiovascular disease (CVD). Advances in EBRT have reduced mean heart dose, but contemporary population-level data on long-term cardiovascular outcomes remain limited. Objective: To examine whether contemporary left-sided EBRT is associated with different long-term CVD risk than right-sided EBRT among women with breast cancer. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases in Ontario, Canada, to identify women who received EBRT after a diagnosis of unilateral breast cancer between April 1, 2002, and December 31, 2017. Patients were followed up through February 28, 2025, for most outcomes and December 31, 2022, for cause-specific mortality. Data analysis was completed in August 2023 (with revisions in August 2025). Exposure: Tumor laterality (left vs right). Main Outcomes and Measures: The primary outcome was hospitalization with a most responsible diagnosis of CVD. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalizations for specific CVD diagnoses, coronary revascularization, and new diagnoses of ischemic heart disease, heart failure, and atrial fibrillation. Cumulative incidence functions estimated the 15-year risk of outcomes accounting for the competing risk of death; event rates per 100 person-years captured recurrent events. Results: Among 76 586 women (mean [SD] age, 59 [12] years; 38 427 [50.2%] with left-sided tumors) followed up for a median (IQR) of 10.9 (7.7-15.2) years, the 15-year cumulative incidence of first CVD hospitalization did not differ by laterality (left: 13.8% [95% CI, 13.4%-14.2%]; right: 13.5% [95% CI, 13.1%-13.9%]; P = .43). In women with preexisting CVD, new diagnoses of heart failure (10.2% [95% CI, 9.9%-10.6%] vs 9.6% [95% CI, 9.2%-10.0%]; P = .01) and ischemic heart disease (13.6% [95% CI, 13.2%-14.0%] vs 12.8% [95% CI, 12.4%-13.2%]; P = .03) were slightly more frequent after left-sided EBRT. The rate of CVD hospitalizations when including recurrent events was modestly higher for left-sided disease (1.72 vs 1.63 per 100 person-years; P = .006). Among women with preexisting CVD, there were no differences in all-cause mortality or recurrent CVD hospitalizations. Conclusions and Relevance: In this cohort study of women treated with EBRT for breast cancer in the past 2 decades, left-sided breast cancer radiation therapy was associated with minimal increases in long-term cardiovascular risk. These findings suggest that contemporary photon-based EBRT techniques have substantially reduced the cardiovascular risk historically associated with left-sided breast cancer radiation therapy.