Cardiovascular morbidity and mortality after radiotherapy for breast cancer: a systematic review and meta-analysis

BACKGROUND: Radiation exposure of the heart secondary to radiotherapy can lead to potential cardiac injury. However, the hazard ratio (HR) for cardiac morbidity and mortality associated with undergoing breast cancer radiotherapy remains unknown. OBJECTIVES: To pool the HRs for cardiovascular risk in patients with breast cancer treated with or without radiotherapy, compare the cardiac risk among irradiated patients divided by the laterality of radiotherapy and further assess the association between the cardiac radiation dose and cardiac morbidity. METHODS: A literature search was conducted using MEDLINE, EMBASE and the Cochrane Library from inception to 1 December 2024. Studies that reported HRs with 95% CIs for the associations of interest were included. Pooled effect estimates were obtained using random-effects meta-analysis. Subgroup analyses were carried out to investigate the influence of the treatment period on cardiovascular outcomes. Publication bias was evaluated using the Egger and Begger's tests. RESULTS: Thirty-one studies involving 610 690 participants were ultimately included. Compared with patients who did not receive radiotherapy, patients who underwent radiotherapy experienced increased risks for developing heart failure (HR: 1.37; 95% CI 1.20 to 1.57). Among patients treated with radiotherapy, left-sided radiotherapy increased the risk of subsequent coronary artery disease (HR: 1.11; 95% CI 1.05 to 1.16). There was a linear correlation between the mean heart exposure dose and cardiac morbidity development (HR: 1.12; 95% CI 1.05 to 1.19). When patients were grouped by treatment period, the risk of cardiac mortality in patients treated with left-sided radiotherapy decreased after 1989 (HR: 1.30 vs 1.02, p<0.01*). No evidence of significant publication bias was identified. CONCLUSIONS: Radiotherapy for breast cancer was associated with an increased risk of experiencing adverse cardiovascular events, which was highly dependent on the cardiac irradiation dose. With advances in radiation techniques, cardiovascular prognosis is expected to improve further.