Two trials reported marginal or no improvement in survival with nodal irradiation in early breast cancer patients, though reductions were seen in recurrence.
Two large trials both reported marginal or no improvement in overall survival (OS) in women with early-stage breast cancer who were treated with regional nodal irradiation in addition to whole-breast irradiation (WBI). However, the addition of nodal irradiation did reduce the risk of recurrence and metastatic disease.
The results of the NCIC Clinical Trials Group MA.20 trial and the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial were published simultaneously in the New England Journal of Medicine.
The MA.20 trial randomized 1,832 breast cancer patients to either WBI at a dose of 50 Gy in 25 fractions or WBI plus nodal irradiation. A median of 12 axillary lymph nodes were removed in each therapy arm. All patients had either node-positive or high-risk localized breast cancer.
At the 10-year follow-up, OS was 82.8% and 81.8% in the nodal irradiation and control groups, respectively (P = .38). The rates of disease-free survival (DFS) were 82.0% and 77.0% (P = .01). The breast cancer mortality rate was similar between the two groups, at 10.3% in the nodal irradiation group and 12.3% in the control group (P = .11).
In the EORTC 22922/10925 trial, 4,004 patients with stage I to stage III primary breast tumors who had undergone mastectomy or breast-conserving surgery, as well as axillary lymph node dissection, were randomized to either WBI or WBI plus nodal irradiation.
At 10-year follow-up, OS was 82.3% and 80.7% in the nodal irradiation and control groups, respectively (P = .06). The rates of DFS were 72.1% and 69.1% (P = .04). The rate of breast cancer mortality was 12.5% in the nodal irradiation group vs 14.4% in the control group (P = .02).
Because these trials began in 2000 (MA.20) and 1996 (EORTC), some of the currently used systemic and radiation therapies-such as trastuzumab and taxane chemotherapies-were not systematically included in the trial protocols.
The treatment regimens were generally well-tolerated, although patients did have an increased risk of pneumonitis, lymphedema, and skin reactions.
“The MA.20 and EORTC trials indicate that some patients benefit from comprehensive nodal irradiation after axillary dissection,” wrote Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston, and Monica Morrow, MD, of Memorial Sloan Kettering Cancer Center in New York City, in their accompanying editorial for both studies.
The major issue is whether patients with one to three nodal metastases and small primary tumors should undergo the additional radiation therapy, they wrote. They also suggested that, based on recent studies, genomic tumor profiling may be able to better predict high-risk patients, as opposed to tumor stage and clinical factors alone.
“[The trials] show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” concluded Burstein and Morrow.