Regional Nodal Irradiation in Early-Stage Breast Cancer

Original Article
Regional Nodal Irradiation in Early-Stage Breast Cancer

Timothy J. Whelan, B.M., B.Ch., Ivo A. Olivotto, M.D., Wendy R. Parulekar, M.D., Ida Ackerman, M.D., Boon H. Chua, M.B., B.S., Ph.D., Abdenour Nabid, M.D., Katherine A. Vallis, M.B., B.S., Ph.D., Julia R. White, M.D., Pierre Rousseau, M.D., Andre Fortin, M.D., Lori J. Pierce, M.D., Lee Manchul, M.D., Susan Chafe, M.D., Maureen C. Nolan, M.D., Peter Craighead, M.D., Julie Bowen, M.D., David R. McCready, M.D., Kathleen I. Pritchard, M.D., Karen Gelmon, M.D., Yvonne Murray, B.Sc., Judy-Anne W. Chapman, Ph.D., Bingshu E. Chen, Ph.D., and Mark N. Levine, M.D. for the MA.20 Study Investigators

N Engl J Med 2015; 373:307-316July 23, 2015DOI: 10.1056/NEJMoa1415340


Background

Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.

Methods

We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.

Results

Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).

Conclusions

Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.)