The risk of major ischemic coronary events was significantly and proportionately associated with the estimated mean radiation dose to the heart in a study of women in Sweden and Denmark who received radiotherapy for breast cancer over a 43-year period.
"The risk of a major coronary event increased linearly with the mean dose to the heart," reported Sarah Darby, Ph.D., of the University of Oxford (England), and her associates. The risk began to increase within the first 5 years of treatment and continued to increase for at least 20 years.
Dr. Sarah C. Darby
The findings make it possible for a woman to estimate her absolute risk of radiation-related ischemic heart disease, the authors wrote. "This absolute risk can be weighed against the probable absolute reduction in her risk of recurrence or death from breast cancer that would be achieved without radiotherapy" (N. Engl. J. Med. 2013;368:987-98 [doi: 10.1056/NEJMoa1209825]).
The population-based study included 2,168 women who had been treated with external-beam radiation for invasive breast cancer between 1958 and 2001, and were enrolled in the Swedish National Cancer Register or the Danish Breast Cancer Cooperative Group. The 963 women who were subsequently diagnosed with a major coronary event (myocardial infarction, coronary revascularization, or death from ischemic heart disease, but not angina) were compared with 1,205 controls.
The major coronary events were diagnosed in the first decade after breast cancer diagnosis in 44% of patients; 33% of events were diagnosed 10-19 years after breast cancer diagnosis; and 23% occurred 20 or more years later. Of the cases, 54% died of ischemic heart disease.
The estimated mean radiation dose to the heart overall was 4.9 Gy (range, 0.03-27.72 Gy). For those with cancer in their left breast, the mean dose exposure to the heart was 6.6 Gy; for those with right-breast tumors, it was 2.9 Gy. Major coronary events were significantly higher among the women with radiation to the left breast.
The estimated dose to the heart of women who are currently treated with radiotherapy ranges from 1 to 5 Gy, the authors said.
For each 1-Gy increase in the mean dose of radiation to the heart, the rate of major coronary events increased by 7.4%, which was a highly statistically significant finding. Compared with controls who had no cardiac dose, the rate of major coronary events increased by 10% among those exposed to a mean radiation dose of less than 2 Gy, by 30% among those exposed to 2-4 Gy, by 40% among those exposed to 5-9 Gy, and by 116% in those exposed to 10 Gy or more.
Among women with a history of ischemic heart disease, the risk of major coronary events was almost sevenfold higher than it was in women with no history of ischemic heart disease. This risk was increased by about 13-fold during the first 10 years after treatment and was about twofold higher in later years.
"Absolute increases in risk for a given dose to the heart were larger for women with preexisting risk factors," they wrote, so "clinicians may wish to consider cardiac dose and cardiac risk factors as well as tumor control when making decisions about the use of radiotherapy for breast cancer."
Among the strengths of the study was that the analysis included all women who were documented as having received radiotherapy for breast cancer in the two countries during the time period studied. The authors cautioned against applying the results to breast cancer patients who are treated before age 30 because few women in this age group were included in the study.
The study was supported by the Oxford University Clinical Trial Service Unit from Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council.