Nick Mulcahy

November 02, 2012

BOSTON, Massachusetts — For women with early breast cancer, radiation to the whole breast does not increase the risk for long-term cardiac toxicity, compared with mastectomy, according to a study with 25-year data, presented here at the American Society for Radiation Oncology (ASTRO) 54th Annual Meeting.

In addition, at 25 years, survival outcomes were similar in women treated with mastectomy and those treated with breast-conserving treatment (BCT), which consisted of radiation and lumpectomy, lead author Charles Simone II, MD, reported at a meeting press conference. He is from the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

These data will "give some comfort to our patients" who receive radiation, said Bruce Haffty, MD, from the Cancer Institute of New Jersey and the Robert Wood Johnson Medical School in New Brunswick, who moderated the press conference.

After 25 years, the survival curves for the 2 treatment groups have begun to separate, and patients treated with BCT have worse outcomes. However, "cardiac toxicity does not seem to be responsible for the slight decrease in patient survival in the BCT arm," Dr. Simone explained.

This study provides a detailed picture of the participants' cardiac anatomy and function. The cardiac results were gathered from 50 of the trial's 102 surviving patients, all of whom are now elderly, when they returned to the National Cancer Institute (NCI) in Bethesda, Maryland for testing 25 years after the trial began. The NCI sponsored the trial.

Of the 50 surviving patients, 26 were from the BCT group and 24 from the modified radical mastectomy group.

"There was absolutely no difference...whatsoever" in toxicity between these 2 study groups, Dr. Simone noted.

Among patients who died after the study started, there was also no difference in cardiac-related causes of death between the 2 groups, according to a review of available death certificates, he added.

The data collection in the study included a detailed cardiac history, exam, and cardiac labs; 3T cardiac magnetic resonance imaging (MRI) to assess anatomic and functional abnormalities; and computed tomography (CT) angiography to evaluate any stenotic coronary disease and to determine the coronary arterial calcium score (a high score is indicative of atherosclerosis).

Dr. Simone pointed out that any would-be cardiac morbidity in the patients had been attenuated with "modern treatment planning." Treating clinicians used CT simulation and 3D planning, he said. A similar trial conducted today would have even better results, he explained, because "newer radiotherapy techniques are even safer for the heart."

This is the first study comparing BCT and modified radical mastectomy to have 25-year data, said Dr. Simone.

Long-term data are valuable because "if you are going to see cardiac toxicity, it will take 10 years," he added.

Original Study

In the original NCI study, 247 patients with stage I to II breast cancer were randomized to modified radical mastectomy or BCT (45.0 to 50.4 Gy whole breast with or without regional nodes, 15.0 to 20.0 Gy boost), and treated from 1979 to 1986 at the NCI.

In addition, node-positive patients (40% of group) received axillary dissection and chemotherapy (doxorubicin and cyclophosphamide for 6 to 11 cycles). After 1985, these patients also received tamoxifen.

The 25-year follow-up study was the brainchild of Nicole Simone, MD, from the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia. She is the sister of Dr. Charles Simone and got to know some of the study participants while working as a resident and rotating through the federal healthcare institutions in Washington, DC (Walter Reed Hospital, Navy Hospital, and NCI).

Dr. Nicole Simone and her colleagues wondered if late pulmonary and cardiac toxicities related to radiotherapy might explain the separation of the survival curves at 25 years.

This led to the launch of the follow-up study. At the ASTRO meeting last year, Dr. Nicole Simone presented the data on pulmonary toxicity. The 2 treatment approaches for early breast cancer have "largely equivalent pulmonary toxicity," she said at the time, as reported by Medscape Medical News.

Now it is Dr. Charles Simone's turn with the cardiac data.

Cardiac Data in Detail

CT angiograms showed that, in BCT patients, there was no difference in atherosclerosis between those whose left breast received radiation therapy and those whose right breast did, Dr. Charles Simone reported. These atherosclerosis data included the left anterior descending coronary artery, which is in close proximity to the chest wall and receives the highest radiation dose.

There was a trend for atherosclerosis in patients from either group who received chemotherapy (hazard ratio, 2.4; P = .07).

Diastolic function, including peak filling rate and diastolic volume recovery, was similar in both groups, as were peak mid-wall strain, chamber mass, volume, and function.

The median coronary arterial calcium score was similar in both groups. No patients exhibited myocardial fibrosis, and 1 patient in each group experienced pericardial thickening.

Among BCT patients, cardiac structure and function were similar for right- or left-breast tumors.

The authors have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 54th Annual Meeting: Abstract 87. Presented October 29, 2012.