The role of postmastectomy chest-wall irradiation in patients with breast cancer classified as pN1 (with involvement of one to three axillary nodes) or pN0 (pathologically node negative) with additional risk factors is uncertain.

In this international, phase 3, randomized trial, we evaluated the omission of chest-wall irradiation in women with "intermediate-risk" breast cancer - defined as cancer that was stage pT1N1, pT2N1, or pT3N0 or stage pT2N0 with a histologic grade of 3, lymphovascular invasion, or both (tumor size: T1, ≤2 cm; T2, >2 cm to 5 cm; or T3, >5 cm) - that was treated with mastectomy, an axillary procedure, and systemic therapy. Patients were assigned to undergo chest-wall irradiation (40 to 50 Gy; the irradiation group) or not to undergo chest-wall irradiation (the no-irradiation group). The primary end point was overall survival, with 10 years of follow-up. Chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis-free survival, causes of death, and radiation-related adverse events were also assessed.

The intention-to-treat population included 808 patients in the irradiation group and 799 in the no-irradiation group. The median follow up was 9.6 years. Overall survival was 81.4% with chest-wall irradiation and 81.9% with no chest-wall irradiation according to 10-year Kaplan-Meier estimates (hazard ratio for death, 1.04; 95% confidence interval [CI], 0.82 to 1.30; P = 0.80). A total of 29 patients had a chest-wall recurrence - 9 (1.1%) in the irradiation group and 20 (2.5%) in the no-irradiation group (between-group difference, <2 percentage points; hazard ratio, 0.45; 95% CI, 0.20 to 0.99). Disease-free survival was 76.2% in the irradiation group and 75.5% in the no-irradiation group (hazard ratio for recurrence or death, 0.97; 95% CI, 0.79 to 1.18), and distant metastasis-free survival was 78.2% and 79.2%, respectively (hazard ratio for distant metastasis or death, 1.06; 95% CI, 0.86 to 1.31).

In this trial, chest-wall irradiation did not result in higher overall survival than no chest-wall irradiation among patients with intermediate-risk, early breast cancer treated with mastectomy and contemporary adjuvant systemic therapy. (Funded by the Medical Research Council and others; SUPREMO ISRCTN Clinical Study Registry number, 61145589.).