The evolution of cardiac changes after breast cancer adjuvant radiotherapy – A six-year follow-up study

Introduction: This prospective study investigated the long-term effects of adjuvant radiotherapy (RT) on cardiac function and biomarkers in early breast cancer patients over a six-year follow-up. Methods: Seventy-three women treated with RT alone, without chemotherapy, were included. Cardiac radiation doses were quantified, and echocardiography and serum biomarkers (high-sensitivity cardiac troponin T [hscTnT] and N-terminal pro-brain natriuretic peptide [proBNP]) were assessed before RT and at three- and six-years post-treatment. Results: Cardiac biomarkers increased significantly during follow-up. Median hscTnT rose from 4 to 6 ng/L (p<0.001), correlating with higher radiation doses to the heart in left-sided patients. ProBNP increased from 78 to 118 ng/L (p<0.001). Left ventricular (LV) systolic function declined in left-sided patients: ejection fraction decreased from 65% to 60% (p=0.002), global longitudinal strain from -18% to -17% (p=0.006), and stroke volume from 74 to 67 mL (p=0.015). Diastolic dysfunction also progressed, with impairments in isovolumic relaxation time and left atrial ejection fraction. Aromatase inhibitor (AI) use and higher mean heart dose were associated with greater cardiac impairment. Conclusion: Subclinical deterioration in cardiac function and elevated biomarkers were evident three years after RT and persisted at six years, suggesting permanent cardiac effects. Both radiation dose and AI therapy contributed to these changes. These findings underscore the importance of long-term cardiac monitoring and support the use of sensitive imaging and biomarkers to detect early radiotherapy-induced cardiotoxicity.