Long-Term Cardiovascular Risk After Radiotherapy in Women With Breast Cancer

Background-Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta-analysis to investigate the link between radiotherapy and long-term cardiovascular morbidity and mortality in patients with breast cancer. Methods and Results-We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% CIs for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-nine studies involving 1 191 371 participants were identified. Patients who received left-sided radiotherapy, as compared with those receiving rightsided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95% CI 1.13-1.48), cardiac death (RR 1.22, 95% CI 1.08-1.37) and death from any cause (RR 1.05, 95% CI 1.01-1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95% CI 1.13-1.49) for coronary heart disease and 1.38 (95% CI 1.18-1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95% CI 36.8-130.5) cases of coronary heart disease and 125.5 (95% CI 98.8-157.9) cases of cardiac death per 100 000 person-years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality. Conclusions-Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.