Attributable fraction of cardiac disease following radiotherapy among breast cancer survivors: a systematic review and meta-analysis

Radiotherapy (RT) is an integral component of cancer treatment; however, it can expose surrounding healthy tissues, including the heart, to ionizing radiation. This study aimed to evaluate the dose-response relationship between mean heart dose (MHD) and cardiac disease and to estimate the attributable burden among breast cancer survivors. PubMed and Embase were searched from inception to 31 January 2026 for studies reporting relative risks (RRs) per gray (Gy). A random-effects meta-analysis was used to pool dose-response estimates. The attributable fraction (AF) and population attributable fraction (PAF) were estimated using pooled dose-response coefficients and representative MHD values. Thirteen studies involving 16 446 breast cancer survivors were included. The pooled RR per Gy increase in MHD was 1.09 (95% confidence interval, 1.05-1.13), with no significant differences across treatment periods. At a representative MHD of 3.39 Gy, the AF among irradiated patients was estimated at 24.3%, indicating that one-quarter of cardiac events may be attributable to radiation exposure to the heart. Assuming a RT utilization of 52.7%, the corresponding PAF among breast cancer survivors was 14.4%. Although MHD decreased from 7.03 Gy before 2000 to 2.57 Gy thereafter, the AF declined from 38.9 to 21.6%. Over the same periods, despite a modest increase in RT utilization (51.1-55.3%), the PAF decreased from 24.5 to 13.2%. Despite these reductions, a measurable burden of cardiac disease remains attributable to radiation, underscoring the importance of minimizing cardiac dose among breast cancer survivors.