The risk of major coronary events rose after radiation therapy by an average of 7.4 percent for every gray (Gy) of exposure to the heart, with no apparent threshold, according to Sarah Darby of the Clinical Trial Service Unit in Oxford, England, and colleagues.
The increase in risk was greatest in the first five years after radiotherapy but persisted for at least two decades, Darby and colleagues reported in the March 14 issue of the New England Journal of Medicine.
Read this story on www.medpagetoday.com.
In addition, women with preexisting cardiac risk factors had greater absolute increases in risk, the researchers reported.
"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," Darby and colleagues concluded.
The study – among 2,168 breast cancer survivors in Sweden and Denmark -- is a wake-up call for physicians, said Dr. Jean-Bernard Durand of the MD Anderson Cancer Center in Houston.
"We have to be extra vigilant with women, making sure we assess them. We make sure they're on correct medicines and we make sure they gain all of the benefits from surviving breast cancer," he told MedPage Today.
Durand noted that in the U.S., women are much less likely than men to receive preventive cardiovascular care; changing that would help to mitigate the risk highlighted by Darby and colleagues.
"Follow their cholesterol, watch for diabetes, manage their blood pressure – all those things can be done to lower their risk of a cardiovascular event," he said.
The study also highlights the importance of good post-cancer follow-up, he said.
Doctors "have an opportunity to intervene in a young woman and really change the course of her life rather than wait for an event and try to change the course of her life when she's older," Durand said.
Radiotherapy for early-stage breast cancer has been shown to reduce both recurrence and death, the researchers noted, but the effect of incidental exposure to the heart has not been clear.
They looked at women with breast cancer who had radiotherapy between 1958 and 2001, including 963 women with major coronary events and 1,205 controls.
Case patients had no recurrence of the breast cancer or incidence of any other cancer before they suffered a major coronary event, defined as myocardial infarction, coronary revascularization, or death from ischemic heart disease.
Controls were matched for country of residence, age at diagnosis, and year of diagnosis, and also had not had a recurrence of their breast cancer or any new malignancy.
Of the major coronary events among women in the study, 44 percent occurred less than 10 years after the breast cancer diagnosis, 33 percent occurred in the next decade, and the remaining 23 percent occurred still later.
The average dose to the heart was 6.6 Gy for women with left breast tumors, 2.9 Gy for those with cancer in the right breast, and 4.9 Gy overall.
While the rate of coronary events rose by 7.4 percent per Gy of exposure, the rate varied with time -- 16.3 percent in the first 5 years after exposure, 15.5 percent in the second 5 years, 1.2 percent in the second decade, and 8.2 percent in later years.
The only tumor characteristic that significantly affected the risk was location, as women with left breast tumors were more significantly likely to be case patients.
The researchers cautioned that few of the women in the study were under 40, so the results may not apply directly to that age group.
In an accompanying editorial in the journal, Dr. Javid Moslehi of Brigham and Women's Hospital in Boston commented that the findings may be the "tip of the iceberg."
"In addition to ischemic cardiac disease," he wrote, "radiation therapy has been associated with other cardiac conditions, including pericardial disease, peripheral vascular disease, cardiomyopathy, valvular dysfunction, and arrhythmias.
Those diseases were not part of the study, nor were those associated with some forms of chemotherapy, he noted.
One implication for practice, he argued, is that the time to look at cardiovascular issues is at the time of breast cancer diagnosis and before treatment starts.