Abstract Body (Do not enter title and authors here):

Background: Radiation therapy (RT) has resulted in significant improvements in breast cancer outcomes, but cardiac morbidity remains an important concern. We evaluated the changes in cardiac function after breast RT and the relationship between cardiac dose metrics and echocardiography-derived measures of cardiac function.

Methods: We performed detailed quantitation of radiation cardiac dose metrics and echocardiographic measures of cardiac function in a prospective longitudinal cohort study of racially diverse women with breast cancer treated at a quaternary healthcare system. Radiation cardiac dose metrics included whole heart, left ventricle (LV), right ventricle (RV) and left anterior descending artery (LAD). Echocardiographic measures included LV ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e’, ventricular-arterial coupling, and RV fractional area change. The mean change in echocardiogram measures from pre-RT, and 6, 12, 24, 36 months post-RT, and the association between cardiac dose metrics and echocardiogram measures, were estimated by repeated measures multivariable linear regression via generalized estimating equations. Analyses were stratified by treatment site (right versus bilateral/left).

Results: 303 participants (33% African American) received adjuvant RT between 2010-2019, and had an echocardiogram performed within three months prior to the start of and after RT. The median mean heart dose (MHD) was 1.19 Gy (Q1-Q3, 0.75-2.61). LVEF increased over time (pre-RT 52.1% to 53.6% at 3 years; p = 0.004), and consistent with this, ventricular-arterial coupling decreased (pre-RT 1.02 to 0.93 at 3 years; p = 0.03). MHD was significantly associated with systolic and diastolic function measures, but the effect sizes were small. For each IQR increase in MHD, there was a 0.31% (95% CI 0.04, 0.57) worsening in longitudinal strain. The maximum LAD dose was associated with multiple echocardiographic parameters, including LVEF (-0.85, 95% CI: -1.58, -0.13), longitudinal strain (0.62, 95% CI: 0.17, 1.08), and circumferential strain (0.64, 95% CI: 0.00, 1.28) for bilateral/left-sided RT.

Conclusion: Modern breast RT was not associated with a clinically important effect on echocardiographic measures of cardiac systolic and diastolic function over a median follow-up of two years. Our findings provide clinically actionable guidance and reassurance regarding the cardiac safety of RT for breast cancer patients in the modern era.