Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer

BACKGROUND: Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment. METHODS: We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged <62 years, treated during 1970-2009. Analyses included proportional hazards models and general population comparisons. RESULTS: CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93-1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9-17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6-2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07-5.69), emerging