BOSTON—Women with early-stage breast cancer who undergo radiotherapy to the whole breast are not at increased long-term risk for cardiac toxicity compared with patients who have modified radical mastectomy, according to a 25-year study reported here at the American Society for Radiation Oncology Annual Meeting (Abstract 87).
While the survival curves for the two groups began to separate after 25 years, “cardiac toxicity does not seem to be responsible for the slight decrease in survival time in the BCT [breast-conserving treatment] arm,” said the study's principal investigator, Charles B. Simone II, MD, Assistant Professor of Radiation Oncology at the Abramson Cancer Center at the University of Pennsylvania.
“Over the past two decades, radiation therapy has become more precise and safer with modern techniques. We are pleased to find that early-stage breast cancer patients treated with modern radiation therapy treatment planning techniques do not have an increased risk of long-term cardiac toxicity and that BCT with radiation should remain a standard treatment option.”
The analysis involved 50 of 102 surviving patients who were treated from 1979 to 1987 in the landmark NCI Breast Conservation Trial and returned for cardiac testing 25 years later.
During the 25 years of follow-up, the mortality curves for the two groups were superimposed. A total of 63 of the 116 women in the mastectomy group died, as did 76 of the 121 in the breast-conservation therapy group—a nonsignificant difference. But after that point, the curves started to separate, leading the researchers to question whether treatment toxicity could account for the separation.
Several small, single-center studies have linked breast radiation to cardiac toxicity, Simone noted. In the original NCI trial, 247 women with Stage I-II breast cancer were randomized to BCT or modified radical mastectomy, both with Level I/II axillary dissection. Patients in the BCT arm received lumpectomy plus radiation with 45.0 to 50.4 Gy to the whole breast with or without regional nodes as needed, and a 15.0 to 20.0 Gy boost to the tumor bed.
“The trial was unique in that patients were treated with modern CT planning—specifically CT simulation with dose inhomogeneity correction—and modern radiation techniques,” he said.
The 40 percent of patients with node-positive disease received axillary dissection plus six to 11 cycles of chemotherapy with doxorubicin and cyclophosphamide. After 1985, postmenopausal node-positive patients also received tamoxifen.
At last year's ASTRO meeting, Simone's sister, Nicole Simone, MD, Assistant Professor of Radiation Oncology at the Kimmel Cancer Center at Thomas Jefferson University, reported that long-term pulmonary toxicity was basically equivalent in the two treatment group.
This year, Charles Simone reported on the long-term cardiac toxicity.
Of the 50 patients in the analysis, 26 were in the BCT group and 24 in the modified radical mastectomy arm. All the patients had a detailed cardiac history and exam and cardiac labs as well as extensive imaging with 3T cardiac magnetic resonance imaging (MRI) to evaluate anatomy and function and computed tomography angiography to look for any coronary artery disease and determine the coronary arterial calcium score. A high score is a sign of atherosclerosis and increased risk of cardiac morbidity, Simone said.
The groups were similar with regard to patient characteristics and exam and lab results. “There were very few coronary events such as myocardial infarction or heart failure and they did not differ between the groups,” he said.
CT angiograms showed that there was no significant difference in the extent of atherosclerosis between the two arms. And in the breast-conserving treatment group, there was no difference in the extent of atherosclerosis “in any segment of any vessel” between the breast that was irradiated and the breast that was not.
There was a trend for patients from either group who received chemotherapy to have visible atherosclerosis.
Diastolic function, including peak filling rate and diastolic volume recovery, as well as peak midwall strain, chamber mass, volume, and function were similar between the two treatment groups. Among BCT patients, cardiac structure and function were similar for right- or left-breast tumors.
The median coronary arterial calcium score was also similar in both groups.
The Bottom Line
“There was absolutely no difference in cardiac toxicity between the two groups,” Simone concluded, adding that he believes that any potential cardiac morbidity had been attenuated with modern treatment planning, CT simulation, and 3D planning.
Patients treated today would have even less of a risk of cardiac toxicity because newer radiotherapy techniques are even safer for the heart, he said.
The moderator of an ASTRO news briefing about interesting breast cancer research reported at the meeting, Bruce G. Haffty, MD, Chair of Radiation Oncology at Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey, said the findings “should give some reassurance to our patients that with modern techniques, radiation does not compromise cardiac function or cause cardiac toxicity.”