Background Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for this interval is unclear. Methods and Results We aimed to study cardiovascular event rates in the first decade following curative radiotherapy for BC. We compared mortality and cardiovascular event rates with an age- and risk factor-matched control population. We included 1095 patients with BC (mean age 56±12 years). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality caused 107 (49.1%) and 22 (10.1%) deaths, respectively. A total of 904 cases were matched to female FLEMENGHO (Flemish Study on Environment, Genes and Health Outcomes) participants. Coronary artery disease incidence was similar (risk ratio [RR], 0.75 [95% CI, 0.48-1.18]), yet heart failure (RR, 1.97 [95% CI, 1.19-3.25]) and atrial fibrillation/flutter (RR, 1.82 [95% CI, 1.07-3.08]) occurred more often in patients with BC. Age (hazard ratio [HR], 1.033 [95% CI, 1.006-1.061], P=0.016), tumor grade (HR, 1.739 [95% CI, 1.166-2.591], P=0.007), and neoadjuvant treatment setting (HR, 2.782 [95% CI, 1.304-5.936], P=0.008) were risk factors for mortality. Risk factors for major adverse cardiac events were age (HR, 1.053 [95% CI, 1.013-1.093]; P=0.008), mean heart dose (HR, 1.093 [95% CI, 1.025-1.167]; P=0.007), history of cardiovascular disease (HR, 2.386 [95% CI, 1.096-6.197]; P=0.029) and Mayo Clinic Cardiotoxicity Risk Score (HR, 2.664 [95% CI, 1.625-4.367]; P<0.001). Conclusions Ten-year mortality following curative treatment for unilateral BC was mainly cancer related, but heart failure and atrial fibrillation/flutter were already common in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for cardiac adverse events. These results suggest a need for early dedicated cardio-oncological follow-up after radiotherapy.

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