Breast cancer is the leading cause of cancer deaths in women in the U.S. Survival is better when breast cancer is diagnosed while still local, and 60.8% of women in the U.S. are diagnosed at this stage. In this group of patients, 5-year survival is 98.5%, according to data from the Surveillance, Epidemiology, and End Results (SEER) Program.1 In these cases, surgical treatment with lumpectomy or mastectomy is often followed by radiation therapy.
In fact, a recent meta-analysis of 22 randomized trials provided additional support for the use of postmastectomy radiation in decreasing the rate of mortality related to recurrent cancer and breast cancer in women found to have 1 to 3 positive lymph nodes during mastectomy and axillary dissection.2 As a result of this and other studies, the need to understand the long-term effects of radiation therapy has become more urgent. One of the most important questions is: Does radiotherapy to the chest increase the incidence of ischemic heart disease (IHD)?
The dose of radiation to the breast and heart is now considerably lower than it has been in the past.3 Nonetheless, when malignancies of the right breast are treated with radiation, the heart is typically exposed to a dose of approximately 1 to 2 Gy. Heart exposure is higher for disease of the left breast, of course, and may run up to 10 Gy.4
A recent study assessed how the dose of radiation a woman receives during breast cancer treatment affects her subsequent risk of IHD.
Darby and colleagues performed a case-control study of major coronary events in women who received external beam radiotherapy for invasive breast cancer.4 Major coronary events were defined as myocardial infarction, coronary revascularization, and death from IHD. Their study, recently published in the New England Journal of Medicine (NEJM), included 2168 women who received radiotherapy for breast cancer from 1958 to 2001 in Sweden and Denmark. Of these, 963 women had major coronary events, and 1205 did not and served as controls. Radiation doses to the whole heart and to the left anterior descending artery were estimated based on radiotherapy records.
Mean radiation dose to the heart was 4.9 Gy (range, 0.03 to 27.72). The rate of cardiovascular events increased by 7.4% for each increment of 1 Gy (95% CI, 2.9 to 14.5;P<.001), with no threshold below which there was no risk. This deleterious effect on the heart started within the first 5 years after therapy and continued for at least 20 years. The presence of cardiac risk factors increased the absolute rate of cardiac outcomes but didn’t affect the proportional increase in the rate of major coronary events per Gy.
None of the women in the study received the cardiotoxic chemotherapeutic agents taxanes or trastuzumab, and very few received anthracyclines, thus minimizing these confounders for ischemic outcomes.
Though radiation delivery techniques have improved considerably in recent decades, the incidental exposure of radiation to the heart is always of concern, and strategies to minimize radiation should be exercised whenever possible. Despite this, as Fei-Fei Liu, MD, Professor of Radiation Oncology at the University of Toronto, stated in an editorial that accompanied the Darby article, “It is important to reassure women with breast cancer that with the use of current technologies, the cardiac dose can be decreased considerably, and cardiac risk factors can be better managed.”
Investigator Sarah C. Darby, PhD, of the Clinical Trial Service Unit at the University of Oxford, England, says that “One thing that our studies have shown rather clearly is that any radiation-related risk probably multiplies the risk that a woman already has. Therefore, women who are already at increased risk of heart disease are likely to be at the greatest risk.”
Dr. Darby and her colleagues provided an example of this in the NEJM article:
- In a 50-year-old woman with no cardiac risk factors at baseline, a 3-Gy dose of radiation to the heart would increase her risk of fatal IHD at age 80 from 1.9% to 2.4% (0.5 percentage points) and her risk of having at least 1 acute coronary event from 4.5% to 5.4% (0.9 percentage points).
- In a 50-year-old woman with at least 1 cardiac risk factor, a 3-Gy dose of radiation would increase her risk of fatal IHD at age 80 from 3.4% to 4.1% (0.7 percentage points) and her risk of having at least 1 acute coronary event by then by 1.7 percentage points.
In their conclusions, Dr. Darby’s team wrote that because the percentage increase in IHD risk per unit increase in the mean radiation dose to the heart was similar in women with and without cardiac risk factors, one could assume that absolute risk increase at a specific dose was larger for women with preexisting cardiac risk factors.
“Therefore, 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,” they wrote.
Significant decreases in the dose exposure to the heart can be achieved by changing the patient’s position (from supine to prone, for example) and the field in which the radiotherapy is delivered.3,5 Silvia C. Formenti, MD, chair of the Department of Radiation Oncology at NYU Langone Medical Center, in New York City, commented, “There are ways to limit dose radiation to the heart beyond what was available in the Darby study.”
Dr. Darby adds, “Published studies of tangential radiation, without irradiation of the internal mammary chain, indicate that for patients treated in the prone position, the heart is usually receiving about 1 to 2 Gy. This is similar to the heart dose delivered to patients treated in the supine position with breathing control. It remains to be seen which of these 2 methods will become more popular with oncologists.”
“Clearly,” she continues, “modern radiotherapy planning systems, including patient-specific CT scans, have the potential to increase the ability of radiation oncologists to control the dose to the heart more precisely than has been possible in the past.”
As these issues are sorted out, Dr. Darby urges clinicians to stay focused: “Remember that the most important thing is to cover the target tissue adequately. Compromising on coverage of the target tissue in order to reduce the dose to the heart is likely to be a risky practice,” she says.