Women who received radiotherapy to treat breast cancers before the mid-1980s had an increased long-term risk of dying of cardiovascular disease, and researchers said the risk may increase with a longer follow-up, even after 20 years post-radiotherapy, according to a study published in the Jan. 25 issue of the Journal of the American College of Cardiology.
While previous trials have shown that breast irradiation can decrease the incidence rate of ipsilateral breast recurrences in women with invasive or in situ breast cancer, long-term survivors can develop cardiovascular toxicity because the radiation dose is delivered to the heart and coronary arteries.
To better evaluate the long-term risks of cardiovascular mortality associated with radiotherapy, Kim Bouillon, MD, MPH, of the Institut Gustave Roussy in Villejuif, France, and colleagues followed the mortality of 4,456 women who survived at least five years after a treatment for breast cancer between 1954 and 1984 at Institut Gustave until the end of 2003, an average of 28 years.
At the time of first treatment, patients had an average age of 55 and more than two-thirds of patients received radiotherapy as part of the primary treatment method.
The researchers reported 421 deaths that were linked to cardiovascular disease—236 were due to cardiac disease. In addition, the authors noted that women who received radiotherapy had a 1.76-fold higher risk of dying of cardiac disease and a 1.33-fold higher risk of dying of vascular disease compared to women who did not receive radiotherapy.
Patients who received radiotherapy without chemotherapy and who underwent lymph node dissection or had an internal breast cancer had a 1.3-fold increased risk of dying from cardiac disease and a 2.1-fold increased risk of dying from vascular disease than those who had no nodal involvement or internal breast cancers.
Bouillon et al found that women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy had a 1.56-fold higher risk of dying of cardiac disease compared with women treated for right-sided breast cancer. “Based on current knowledge, this excess risk, if confirmed, is unlikely to be attributable to low doses (less than 1 Gy) of radiation to the heart delivered during radiotherapy limited to the right breast, but rather to radiotherapy delivered to the IMC [internal mammary chain] for right-sided breast cancer during which part of the heart is included in the radiotherapy fields,” the authors wrote.
“Indeed, to date, apart from the notable exception of a study on U.S. nuclear workers, there is no compelling evidence of an increase in cardiovascular diseases for radiation doses below 5 Gy; in other words, the average heart dose that is not usually reached during radiotherapy is limited to the right breast,” the authors noted.
In an accompanying JACC editorial, Ronald M. Witteles, MD, of the Stanford University School of Medicine in Stanford, Calif., wrote, “[I]t is impossible to believe that the real advances in radiation techniques over the last three decades have not made a difference in acquired cardiac morbidity/mortality. However, the extent of the impact is unknown—and impossible to know—at this point.”
While Witteles offered that prone positioning can decrease cardiac radiation dose in some, it may increase it in others and depends on patient anatomy. These data however, prove that physicians must evaluate whether or not to irradiate the internal mammary chain nodes due to the substantial radiation involved.
“Radiation therapy clearly should not be thrown out with the proverbial bathwater—but considering the data, we must approach the issue with eyes wide open. Buyer beware.”