Elective Internal Mammary Node Irradiation in Women With Node-Positive Breast Cancer: Results of a Randomized, Phase 3 Trial

Purpose/Objective(s) The sole benefit of internal mammary area irradiation (IMNI) on treatment outcome is unknown. We examined whether the inclusion of IMNI in regional nodal irradiation improved outcomes in women with node-positive breast cancer. Materials/Methods KROG 08-06 is a multicenter, prospective, randomized phase 3 trial done at 13 hospitals in South Korea. Patients with pathologically confirmed node-positive breast cancer after breast conservation surgery (BCS) or mastectomy with axillary lymph node dissection were eligible. Patients with distant metastasis or those who had neoadjuvant treatment were excluded. All patients underwent regional nodal irradiation along with breast or chest wall irradiation using 3-dimensional conformal radiotherapy with a total dose of 45–54 Gy and fractional dose of 1.8–2.0 Gy. Patients were stratified according to the type of surgery (BCS or mastectomy) and N stage (N1 or N2, N3) and randomly allocated to either IMNI or no IMNI. The primary endpoint was 7-year disease-free survival (DFS). Secondary endpoints were rates of overall survival, breast cancer-specific survival, and toxicity. Results Between 2008 and 2013, 747 patients were enrolled, of whom 362 patients in IMNI arm and 373 patients in non-IMNI arm were analyzed. Nearly all patients underwent taxane-based adjuvant systemic treatment. At a median follow-up of 8.4 years, 127 patients had breast cancer-related events and 89 patients died. At 7 years, the DFS rates were 81.9% in non-IMNI arm and 85.3% in IMNI arm (HR, 0.80; 95% CI, 0.57–1.14; P = .220). Subgroup analyses showed significantly improved DFS and breast cancer mortality in IMNI arm among the patients with medio-centrally located tumors. In this subgroup, the 7-year DFS rates were 81.6% without IMNI versus 91.8% with IMNI (HR, 0.42; 95% CI, 0.22–0.82; P = .010) and the 7-year breast cancer mortality rates were 10.2% versus 4.9% (HR, 0.40; 95% CI, 0.17–0.99; P = .048). There were no differences in adverse effects including cardiac toxicity and radiation pneumonitis between treatment arms. Conclusion Including IMNI in regional nodal irradiation did not significantly improve DFS for unselected women with node-positive breast cancer. Women with medially or centrally located tumors can be considered for applying IMNI when performing regional nodal irradiation.