Radiotherapy Increases Risk of Heart Disease in Some Women With Breast Cancer

Sarah Darby, PhD

While radiotherapy can be an effective treatment for early-stage breast cancer, incidental irradiation of the heart during treatment may increase the risk of developing ischemic heart disease, according to a recent study.¹ The researchers explained that the risk is small for most women, however, and that their study should actually help physicians identify patients for whom radiotherapy is most appropriate.

“We carried out this work because doctors could not reliably estimate the risk of heart disease in women treated with radiotherapy for breast cancer. Doctors can now estimate the risk and know that in most cases it will be very small so that they can reassure their patients. In addition, the few women for whom radiotherapy poses undue risk can now be identified, so that alternative techniques can be considered,” said lead author Sarah Darby, PhD, University of Oxford, in a statement.

Darby and colleagues’ population-based analysis looked at major coronary events (defined as myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women in Sweden and Denmark who received radiotherapy for breast cancer between 1958 and 2001. Of those women, 963 had experienced major coronary events, while the other 1205 served as controls. The researchers estimated the mean radiation doses to the whole heart and to the left anterior descending coronary artery from information on each patient’s radiotherapy chart.

The researchers found that the overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03- 27.72), with mean doses of 6.6 Gy for women with tumors in the left breast and 2.9 Gy for tumors in the right breast. Exposure at 1 Gy is enough to raise the risk of ischemic heart disease, the researchers noted.

In the study, the rate of major coronary events increased by 7.4% for each increase of 1 Gy of radiation that the heart received (95% CI, 2.9-14.5; P <.001). When the authors grouped women based on whether the mean radiation dose to the heart was less than 2 Gy, 2 to 4 Gy, 5 to 9 Gy, or ≥10 Gy, the percentage increases of major coronary events compared with the estimated rate if the dose of radiation had been 0 were 10% (95% CI, -9 to 33), 30% (95% CI, 14-49), 40% (95% CI, 15-72), and 116% (95% CI, 59-195), respectively.

According to the researchers, no significant difference was observed in the percentage increase per Gy when accounting for matching factors used in the selection of controls, tumor characteristics, or cancer treatments that were given in addition to radiotherapy. A higher rate of major coronary events was observed in women with cardiac risk factors compared with those who did not have such risk factors, but the percentage rate increase in the rate of major coronary events per Gy was similar for women with or without those risk factors at the time they were diagnosed with breast cancer.

The authors noted that a limitation of the study was the fact that individual computed tomography (CT)—based information on radiotherapy was not available for the women studied because they were treated prior to when threedimensional CT-based planning was being implemented for radiotherapy. However, using data from CT-based planning scans, they found that the patient-to-patient variation in mean radiation dose to the heart is minimal.

In an accompanying editorial, Javid Moslehi, MD, codirector of the Cardio-Oncology Program at Brigham & Women’s Hospital and instructor in the Department of Medicine at Harvard Medical School/Dana-Farber Cancer Institute, wrote that this study may represent “just the tip of the iceberg” in the link between cardiac issues and radiotherapy, since radiation therapy has been associated with other cardiac conditions that were not included in this study, including pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias.²

“Given the widespread use of radiation therapy in the treatment of breast cancer, and the continually expanding arsenal of novel therapies, the current study calls for greater collaboration between oncologists and cardiologists,” Moslehi wrote. “An important lesson for the oncologist may be that the time to address concerns about cardiovascular ‘survivorship’ is at the time of cancer diagnosis and before treatment rather than after completion of therapy.”

References

1. Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368(11):987-998.
2. Moslehi J. The cardiovascular perils of cancer survivorship [editorial]. N Engl J Med. 2013;368(11):1055-1056.