CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.
In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.
After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.
"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.
The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.
Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.
The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.
"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.
He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.
There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.
Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."
The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).
The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.
In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.
After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.
"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.