Women with early sentinel lymph node-positive breast cancer achieve as much of a disease-free and survival benefit from axillary radiotherapy as they do from axillary lymph node dissection with significantly less risk of lymphedema.
Emiel J. Rutgers, MD
Women with early sentinel lymph node-positive breast cancer achieve as much of a disease-free and survival benefit from axillary radiotherapy (ART) as they do from axillary lymph node dissection (ALND) with significantly less risk of lymphedema, according to clinical trial results presented June 3 at the American Society of Clinical Oncology (ASCO) Annual Meeting.
The findings of the phase III AMAROS trial align with the gradual move away from reliance upon surgery in managing early breast cancer and are likely to be embraced in the United States by patients and oncologists alike, research leaders said in discussing the data.
“When we designed this study to lessen the toxicity of primary breast cancer treatment 12 years ago, axillary clearance was dogma,” said lead investigator Emiel J. Rutgers, MD, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, in discussing the findings at a press conference and an interview.
He said oncologists in the Netherlands, where the trial was conducted, already have started incorporating its findings into clinical practice.
Andrew D. Seidman, MD, an attending physician for the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York, said the study would influence treatment for women with early breast cancer, a group that makes up approximately 80% of the 230,000 new cases diagnosed in the United States annually. “This is going to represent a new option for patients, other than having full clearance of their axillary lymph nodes,” said Seidman, who served as an ASCO commentator on the study.
In the study, 4806 patients with primary tumors up to 5 cm that were clinically node-negative (cT1-2N0) were recruited from 2001 through 2010. The patients underwent sentinel node biopsies and, depending upon the results, either received follow-up monitoring or were randomized to ART versus ALND.
The follow-up group included 3381 patients with no evidence or minimal cancer spread. The treatment arms consisted of 681 patients who received ART and 744 who went on to ALND.
After 5 years’ follow-up, the rates of cancer recurrence in the axilla were very low for both groups, a finding Rutgers said was surprising to investigators who had designed the trial so many years earlier. The recurrence rate in the ART group was 1.03% (7 patients), compared with 0.54% (4 patients) in the ALND group.
The rate of recurrence was so low in both groups that the study turned out to be underpowered for assessing noninferiority between the two treatments, which was one of its original goals, according to the abstract. The axillary recurrence rate after a negative sentinel node biopsy was 0.8% (25 of 3131 patients).
There were no significant differences in the estimated 5-year disease-free survival between ART and ALND (82.7% vs 86.9%, respectively; P = .18) or in overall survival (92.5% vs 93.3%, respectively; P = .34).
However, lymphedema measured as any symptom and/or treatment such as a sleeve garment was significantly lower in the ART group. For those who had ART, the rate of lymphedema was 22% in the first year and 14% at 5 years. By contrast, the rates in the ALND group were 40% in the first year and 28% at 5 years.
There was a trend toward more shoulder movement impairment at 1 year with ART, but it was not statistically significant and had disappeared in the follow-up conducted at 3 years and 5 years, Rutgers said.
Andrew D. Seidman, MD
The lower incidences of toxicity did not translate into a statistically significant advantage for ART in quality-of-life surveys conducted at 1, 3, and 5 years, Rutgers said. He suggested the questionnaires themselves might not have accounted enough for lymphedema.
Seidman said he believed patients with breast cancer and oncology specialists are becoming more comfortable with less aggressive strategies for early breast cancer.
“We’re fairly mature already in terms of understanding and transitioning to the idea that less surgery for the axilla is important,” Seidman said. “Initially, it was only patients with negative sentinel lymph nodes who were considered to be safe to have less surgery.
“Here, we’re not asking patients who have a limited number of lymph nodes to do nothing,” Seidman added. “We’re simply showing them that there’s an alternative to surgery, and it’s radiation with less downstream side effects and toxicities.”
Rutgers EJ, Donker M, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial (10981/22023). J Clin Oncol. 2013;31 (suppl; abstr LBA1001).