Nodal irradiation improved breast cancer disease-free but not overall survival

Although the MA.20 and EORTC trials showed that regional nodal irradiation was generally well tolerated, greater risks of lymphedema, pneumonitis, and cutaneous reactions were observed.

In spite of these concerns, the MA.20 and EORTC trials indicate that some patients benefit from comprehensive nodal irradiation after axillary dissection. Treatment selection for the individual patient is the key issue. At the extremes, there is relatively little controversy. There is no rationale for nodal irradiation in patients with negative axillary nodes because nodal recurrence rates after negative results on sentinel-node biopsy are less than 1%, and isolated internal mammary metastases are very uncommon, even in patients with medial tumors. Conversely, a heavy tumor burden, as shown by metastases to four or more lymph nodes or extracapsular extension beyond the lymph nodes, is a strong predictor of increased risk, suggesting the need for nodal irradiation. The dilemma resides among patients with one to three nodal metastases, particularly when such findings are associated with a small primary tumor (< 5 cm), and parallels the controversy over postmastectomy radiotherapy in this group. Postmastectomy radiotherapy has been shown to improve survival for women with one to three affected axillary lymph nodes but only in the context of a 5-year local-regional recurrence rate of 17%, far in excess of current rates. With the use of clinicopathologic characteristics to selectively offer postmastectomy radiotherapy, 5-year local-regional recurrence rates of 3%-4% without radiotherapy are observed, and the majority of women are able to avoid radiotherapy. By extrapolation, we would consider regional nodal irradiation for patients with one to three lymph node metastases only when other adverse prognostic factors are present. These factors include an age under 50 years and tumor characteristics such as extensive lymphovascular invasion, a high histologic grade, an unfavorable molecular profile, and large size.

Dr. Harold J. Burstein is with Dana-Farber Cancer Institute, Brigham & Women’s Hospital, and Harvard Medical School, Boston, and Dr. Monica Morrow is with Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York. These remarks were excerpted from an accompanying editorial (N. Engl. J. Med. 2015 Jul 23 [doi:10.1056/NEJMe1503608]).