Left atrial and left ventricular radiation exposure predict long-term cardiovascular events after breast cancer radiotherapy

Background Adjuvant breast cancer (BC) radiotherapy (RT) improves survival and local control, but cardiovascular (CV) toxicity remains a concern. Aim This retrospective study investigated the association between RT doses to cardiac substructures and CV toxicity 15 years after BC RT. Methods Women with unilateral BC diagnosed between 2007 and 2008, treated with RT at [Anonymous] were retrospectively included. Patients with major adverse cardiac events (MACE) were matched to controls by CV risk factors, anthracycline and anti-HER2 therapy. Cardiac substructures were delineated on simulation scans, and multivariable logistic regression was performed to assess associations between RT doses to these substructures and MACE or other CV events. Results After a median follow-up of 16.5 years (IQR 16.1–17.1), and inclusion of 878 patients, 173 patients experienced MACE and were matched to 167 controls. All patients underwent adjuvant RT using 3-dimensional conformal RT to a total dose of 50 Gy in 25 fractions, with or without a boost to the tumor bed. New individual cardiac toxicities included: atrial fibrillation (AF) 98/878 (11.16%), heart failure (HF) 82/878 (9.34%), coronary artery disease (CAD) 46/878 (5.24%) and valvular disease 180/878 (20.50%). Mean heart doses were 6.62 ± 5.20Gy (MACE) and 5.76 ± 4.96Gy (controls) ( p = 0.0916). Compared with controls, patients with MACE had significantly higher disease stage and more frequent histories of CAD, AF and HF. Maximum RT doses to the left atrium (LA) were associated with MACE, new-onset HF, AF and valvular disease, while mean RT dose to the left ventricle (LV) was associated with development of CAD (all p < 0.05). Conclusion This study demonstrates that patients treated with RT for BC may experience diverse CV toxicities during long-term follow-up. Higher doses to left-sided cardiac substructures, particularly the LA and LV, were associated with specific CV endpoints, while MHD was not associated with toxicity.