Practice-Changing Radiation Study in Early Breast Cancer?

Focus on 1-3 Positive Nodes

June 04, 2011

June 4, 2011 (Chicago, Illinois) — Women with early breast cancer and as few as 1 to 3 positive nodes should be offered radiation treatment to their regional lymph nodes, in addition to standard whole-breast radiation (WBI), according to a study presented here at the American Society of Clinical Oncology (ASCO®) 2011 Annual Meeting.

Dr. Timothy Whelan

In a phase 3 clinical trial of women with either node-positive or high-risk node-negative breast cancer, regional nodal irradiation (RNI) significantly improved disease-free survival at 5 years (hazard ratio [HR], 0.67; P = .003), said lead author Timothy J. Whelan, BM, BCh, from McMaster University in Hamilton, Ontario, Canada.

This constituted a 33% improvement in disease-free survival in the group receiving WBI plus RNI, compared with the group receiving the WBI alone.

This is a "potentially practice-changing" clinical trial, Dr. Whelan told Medscape Medical News at an ASCO press conference where the study was highlighted.

However, these are interim, 5-year results, said Dr. Whelan. The study's primary outcome of overall survival has not yet seen a statistically significant improvement, but there is a trend present, he said.

Overall mortality was reduced by 24% in the group receiving WBI plus RNI, compared with WBI alone group (HR, 0.76; 5-year risk, 7.7% and 9.3%, respectively; P = .07).

Dr. Whelan presented the results on behalf of the National Cancer Institute of Canada Clinical Trials Group and American and Australian clinical trials groups, all of which conducted the study, known as MA.20.

Notably, 85% of the 1832 study participants had 1 to 3 positive nodes; the benefit of adding RNI in such women has been unclear, he said.

At the press conference, Dr. Whelan explained that, in general, women with node-positive breast cancer are treated with breast-conserving surgery plus axillary lymph node dissection, followed by WBI.

However, if a woman's cancer has high-risk features, such as a tumor larger than 5 cm or more than 3 positive axillary nodes, she often also receives RNI, which is defined as radiation to the internal mammary, supraclavicular, and axillary lymph nodes; this is the course of treatment recommended in the ASCO guidelines.

Women with 1 to 3 positive nodes have constituted a gray zone of uncertainty and have been in need of further study, Dr. Whelan summarized.

Practice Changing: 2 Votes

Some clinicians have already adopted RNI as part of their standard of care for all node-positive women, including those with 1 to 3 positive nodes.

"As an institutional policy, we have routinely done RNI in these patients for some years," said David E. Wazer, MD, from Rhode Island Hospital and Brown University in Providence.

Dr. Wazer told Medscape Medical News that all node-positive women should receive RNI and that the study should be practice changing.

Another radiation oncologist called the study "intriguing," but suggested that clinicians make RNI decisions in patients with 1 to 3 positive nodes on a case-by-case basis.

"This has been an area of controversy, with data to both support and not support the addition of regional nodal radiation in this subset of patients," Sandy Anderson, MD, from Fox Chase Cancer Center in Philadelphia Pennsylvania, told Medscape Medical News.

The MA.20 data are important, said Dr. Anderson, in the context of another study of women with 1 to 3 positive axillary lymph nodes, the Z0011 trial from the American College of Surgeons, which was presented last year at the ASCO annual meeting. That study found that "whole-breast radiation is adequate treatment after positive sentinel lymph node biopsy" in women with 1 to 3 positive nodes, and was not inferior to completion axillary dissection, said Dr. Anderson.

Just how much treatment a patient with 1 to 3 positive nodes needs is a complex calculation, according to Dr. Anderson. "Clinicians need to weigh the toxicity of regional nodal radiation against the toxicity of further axillary dissection, along with the clinical and pathologic factors for each individual patient," she said.

Findings

The women in the MA.20 study, who averaged 53 years in age, had all been treated with breast-conserving surgery and adjuvant systemic therapy — either chemotherapy (91%) or endocrine therapy (71%). As noted above, most had 1 to 3 positive nodes, but a small proportion of the women had either more than 4 positive nodes (5%) or high-risk node-negative breast cancer (10%).

The study design randomized the women to receive either WBI alone (n = 916) or WBI plus RNI (n = 916).

The WBI consisted of 50 Gy in 25 fractions plus boost irradiation. The RNI consisted of 45 Gy in 25 fractions.

There is now a median follow-up of 62 months. Dr. Whelan explained that the study had a protocol-specified interim analysis of relapse patterns, survival, and toxicity at 5 years. After review of the data, the Data Safety Monitoring Committee recommended the release of the results.

In addition to the overall disease-free survival benefit, there were other statistically significant benefits for the group receiving the RNI therapy, said Dr. Whelan.

WBI plus RNI, compared with WBI alone, was associated with a statistically significant 42% improvement in isolated locoregional disease-free survival (HR, 0.58; 5-year risk, 3.2% and 5.5%, respectively; P = .02), and a 36% improvement in distant disease-free survival (HR, 0.64; 5-year risk, 7.6% and 13.0%, respectively; P = .002).

On the downside of the data, WBI plus RNI, compared with WBI alone, was associated with a statistically significant increase in dermatitis (50% and 40%, respectively; P < .001), grade 2 or greater pneumonitis (1.3% and 0.2%, respectively; P = .01), and lymphedema (7.3% and 4.1%, respectively; P = .004).

The rate of lymphedema with RNI seems low, said Dr. Wazer. "Community experience may see a higher rate," he added.

The authors have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO®) 2011 Annual Meeting: Abstract LBA1003. To be presented June 6, 2011.

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