BREAST IRRADIATION INCREASES CARDIOVASCULAR RISK
Women exposed to ionizing radiation when they receive radiotherapy as part of their treatment for breast cancer have an increased risk for heart disease. A new study, published in the March 14 issue of the New England Journal of Medicine, quantifies this risk.
Researchers learned from Hiroshima and Nagasaki that ionizing radiation induces cardiovascular events, such as myocardial infarction, senior researcher Per Hall, PhD, professor of radiation epidemiology at the Karolinska Institutet in Stockholm, Sweden, told Medscape Medical News.
"Oncologists have always suspected that ionizing radiation for breast cancer, particularly for left-sided breast cancer, increases the risk of myocardial infarction," Dr. Hall said.
"What we haven't known is at what dose this risk increases. Nor have we understood how previous disorders influence this risk," he added.
Dr. Hall and his group conducted a population-based case–control study of major coronary events, including myocardial infarction, coronary revascularization, and death from ischemic heart disease, in 2168 women who had received radiotherapy for breast cancer from 1958 to 2001 in Sweden and Denmark.
Of these women, 963 had major coronary events and 1205 did not. Forty-four percent of the coronary events occurred less than 10 years after breast cancer was diagnosed, 33% occurred 10 to 19 years after, and 23% occurred 20 or more years after.
Irradiation for cancer of the left breast was associated with higher rates of major coronary events than irradiation of the right breast (P = .002). However, there was no link between major coronary events and characteristics of the tumor or the chemotherapy received to treat the breast cancer.
The mean radiation dose to the heart was 4.9 Gy (range, 0.03 to 27.72 Gy). The researchers found that major coronary events increased as the mean dose to the heart increased.
For women with tumors in the left breast, the estimated mean dose of radiation to the heart was 6.6 Gy; for those with tumors in the right breast, it was 2.9 Gy.
Each 1.0 Gy of radiation was associated with a 7.4% increase in the occurrence of a subsequent major coronary event (95% confidence interval [CI], 2.9 - 14.5; P < .001).
The researchers also found that the risk for a major coronary event increased in the first 5 years after exposure to radiation. This risk continued out to 3 decades after radiotherapy.
Women with a history of ischemic heart disease were at greater risk for a major coronary event than those with no such history (overall rate ratio, 6.67; 95% CI, 4.37 - 10.18).
This risk was highest in the first 10 years after the cancer diagnosis (rate ratio, 13.43; 95% CI, 7.65 - 23.58); during later years, the rate ratio was 2.09 (95% CI, 1.05 - 4.13; P < .001).
Women with a history of circulatory diseases, diabetes, or chronic obstructive pulmonary disease also had higher rates of major coronary events, as did those who smoked, had a high body mass index, or a history of regular analgesic use.
Dr. Hall pointed out that many people would argue that the radiation doses to the heart are lower today than they used to be. Although this is true, many of the drugs developed to treat breast cancer are themselves cardiotoxic, including older chemotherapy compounds, such as anthracyclines.
"In this project, we were not able to study the combined effect of radiotherapy and cardiotoxic compounds due to the low number of women who were treated more recently," he said.
Dr. Hall also noted some of the study limitations.
"The major limitation was that, in order to have a long follow-up, we mostly included women who were treated more than 10 years ago. This means that we do not know how today's treatments are affecting women," he explained.
The strengths of the study are the complete follow-up, the detailed information on doses (which Dr. Hall considers to be truly unique), and the thorough verification of outcome. "We are certain that women who developed myocardial infarction did in fact have this diagnosis," he said.
For now, doctors can tell their patients that radiotherapy is a very important treatment and it should be used, he noted. However, they should try to lower the dose of radiation to the heart as much as possible. "They should also think twice before they administer radiotherapy to women who previously had a myocardial infarction," he said.
Dr. Hall hopes that this study will have an impact on the way doctors treat their breast cancer patients. "Given the increasing incidence of breast cancer and the decreasing mortality, more and more women are living cured of their cancer. Late adverse health effects do become an increasing problem. We hope our data can be used to help clinicians guide their treatment decisions when deciding whether a woman will actually benefit from radiotherapy, especially if she has a history of heart disorders or risk factors for myocardial infarction," he explained.
Tip of the Iceberg?
In an accompanying editorial, Javid Moslehi, MD, from Harvard Medical School in Boston, Massachusetts, writes that the findings by Dr. Hall and his group could be "just the tip of the iceberg."
"In addition to ischemic cardiac disease, radiation therapy has been associated with other cardiac conditions, including pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias — diseases that were not included in this analysis," Dr. Moslehi explains.
He agrees with Dr. Hall that newer therapies have increased survival in breast cancer, and points out that "cardio-oncology (cardiovascular care of patients with cancer) has emerged as a new discipline in medicine."
Dr. Moslehi also calls for greater collaboration between cardiologists and oncologists because the use of radiation therapy in the treatment of breast cancer is so widespread.
"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," he writes.
"Similarly, cardiologists need to assess prior exposure to radiation therapy as a significant cardiovascular risk factor in survivors of breast cancer," he adds.
The study was supported by Cancer Research UK, the British Heart Foundation, the UK Medical Research Council, the European Commission, the UK Department of Health, the British Heart Foundation Centre for Research Excellence, and the Oxford National Institute for Health Research Biomedical Research Centre. Dr. Hall has disclosed no relevant financial relationships. Dr. Moslehi reports financial relationships with Novartis and Forest Laboratories.
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