BY PETER GOODWIN
CHICAGO -- In women with early breast cancer who were clinically node negative but with a positive sentinel node, complete axillary clearance was not found to be superior to use of radiotherapy, which also had the benefit of being less toxic. The final analysis of the European Phase III EORTC AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery?) trial, were reported here at the American Society of Clinical Oncology
Annual Meeting (Abstract LBA1001) by Emiel J.T. Rutgers MD, PhD, head of the department of surgery at the Netherlands Cancer Institute.
The results also showed that patients treated with radiotherapy were only half as likely to develop lymphedema as compared with those having surgery.
The aim of the study, he explained in an interview, was to see if there was a way to lessen the toxicity of surgical clearance of lymph nodes when metastases are found in the sentinel node but were not detectable clinically: “When we designed the study 12 years ago axillary clearance was dogma for these patients,” he said, noting, though, that there was also recent interest in looking at other approaches to treating sentinel node positivity.
The researchers were concerned about the high level of side effects from lymph node surgery -- particularly obstruction of the lymphatics of the arm, which usually necessitates lifelong treatment to manage lymphedema necessary.
The study included 4,806 patients with clinically node-negative early breast cancer, 3,382 of whom had no or only minimal metastasis and were allocated to follow-up. A total of 744 of the remaining 1,425 patients were allocated to surgery and 681 patients to radiotherapy. No significant differences in five-year overall survival (92.5 and 93.3 percent) emerged between the two treatment groups. Disease-free survival rates were also similar (82.6 and 86.9 percent).
The rate of cancer recurrence in the axilla was very low in both groups: 0.54 percent (4/744 patients) for surgery and 1.03 percent (7/681) for radiotherapy.
Arm edema (measured as any incidence of any symptom and/or treatment) was double -- at 28 percent -- in the group allocated to complete axillary dissection as compared with 14 percent in those treated with radiotherapy.
In terms of quality of life and shoulder movement impairment there were no significant differences between the study arms. “Radiotherapy to the axilla is a good alternative to surgical removal of the lymph nodes,” Rutgers said. “If treatment is deemed necessary [in T1/T2 N0 breast cancer] radiotherapy, is better than surgery.”
With a median follow-up of only 6.1 years, however, the long-term toxicity comparison remains to be determined, but Rutgers said he was fairly confident that those results will still favor radiotherapy. “In the long run the downside of using radiotherapy could be a small risk of damage to the nerves to the arm – plexopathy -- and radiation-induced sarcomas,” he said. But there has been no sign of such nerve damage yet, he noted, estimating that even if there was, the incidence of serious damage was not likely to exceed one percent of serious damage at 10 years.
Lymphedema, on the other hand, was a different situation: “Lymphedema in the long run is associated with serious side effects and very rare but serious sarcoma of the arm, and if you prevent lymphedema, you may prevent that serious side effect in the long run.”
For cancer doctors the recommendation is quite clear, he said: “First, do sentinel node. Second, think what you do with the outcome -- if it’s negative, do nothing; if positive – if there is a small primary tumor -- you can refrain from any axillary treatment. If there’s more involved tumor, then radiotherapy is now the standard of care instead of a axillary clearance.
In early breast cancer, axillary clearance -- complete axillary dissection -- is obsolete.”
The moderator of a news conference that included the study, Andrew D. Seidman MD, of Memorial Sloan-Kettering Cancer Center, and a member of ASCO’s Cancer Communications Committee, noted that big steps have been made recently in the treatment of early breast cancer: “In the last few years we’re re-thinking the local-regional management of breast cancer, with less surgery and perhaps now an increased consideration for the role of radiotherapy for local control.”
Only for Defined Population
Asked for her opinion for this article, Pat Price, MD, Visiting Professor of Oncology at Imperial College in London and Chairperson of the UK’s Action Radiotherapy charity, said that for this defined population of women (T1/T2 breast cancer, clinically node-negative with positive sentinel node biopsy) the AMAROS findings are grounds for change: “For this small group of patients surgery would not necessarily be the right option,” she said.
“Axillary surgery will still be required for other groups of patients and there’s a lot of work to be done about selecting those who need axillary node clearance, or perhaps those who don’t need any surgery or radiotherapy at all.”
Price said she was impressed by the size of the AMAROS study but had some reservations about the current definitions of lymphedema, which she said has been poorly studied and still needs to be researched: “We’ve got some very crude measurements of it and definitions of it. We don’t even understand the mechanism.”
Still, she called the reduction of lymphedema “startling” – “That’s really important, because lymphedema is a huge problem -- long term -- for patients, and takes up a lot of health care costs -- and there is also the worry that patients have about lymphedema. Since we’ve been doing more clearances, lymphedema has become a bigger problem. So if we can reduce this, this will be fantastic for women,” she said.