Risk of Ischemic Heart Disease in Women After Radiotherapy for Breast Cancer

Study Questions:

Does radiotherapy for breast cancer increase subsequent risk of ischemic heart disease?


This was a population-based case-control study of women who underwent radiotherapy for breast cancer in Sweden and Denmark. In Sweden, all women living in Stockholm for whom data were recorded in the Swedish National Cancer Register, who had a diagnosis of breast cancer between 1958 and 2001, were younger than 70 years of age at the time of diagnosis, and had received radiotherapy. In Denmark, all women for whom data were recorded in the register held by the Danish Breast Cancer Cooperative Group were considered for the study if they received the diagnosis of breast cancer between 1977 and 2000, were younger than 75 years at the time of diagnosis, and received radiotherapy. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. The primary outcome of interest was major coronary events including myocardial infarction, coronary revascularization, or death from ischemic heart disease.


A total of 2,168 women in the cohort included 963 women with major coronary events and 1,205 controls. The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03-27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per Gray (95% confidence interval, 2.9-14.5; p < 0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per Gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.


The investigators concluded that exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with pre-existing cardiac risk factors have greater absolute increases in risk from radiotherapy than other women.


These data provide clinically useful information for women undergoing radiation for breast cancer. In particular, women with pre-existing cardiovascular risk factors may wish to monitor cardiovascular risk factors and modify risk factors that are not well controlled.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Myocardial Infarction, Myocardial Ischemia, Case-Control Studies, Radiation, Ionizing, Sweden, Denmark

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