Outcomes Following Salvage Radiation and Systemic Therapy for Isolated Locoregional Recurrence of Breast Cancer after Mastectomy: Impact of Constructed Biologic Subtype

PURPOSE: This study examines factors associated with outcomes following salvage radiation and systemic therapy for breast cancer patients who developed isolated locoregional recurrence (ILRR) after mastectomy alone, while focusing on the prognostic significance of constructed biologic subtype in this setting. METHODS AND MATERIALS: 269 postmastectomy patients in total treated for ILRR were included. Cumulative incidence of locoregional control (LRC), distant metastasis (DM)-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated using Kaplan-Meier method. For statistical analysis, biologic subtypes were constructed from hormonal receptors (Rec) and HER2, consisting of Rec+/HER2-, Rec+/HER2+, Rec-/HER2+, and Rec-/HER2-. The association of clinic-pathological and treatment-related parameters with outcomes was evaluated using a Cox regression model. RESULTS: At a median follow-up of 65 months, 56 (20.8%) patients failed to secure LRC after radiotherapy, and 165 patients (61.3%) developed DM. Overall, the actuarial 5-year LRC, DMFS, DFS, and OS rate was 77.3%, 45.6%, 43.9%, and 66.8%, respectively. Multivariate analysis revealed that constructed biologic subtype represented the most significant prognostic factor for any outcome. Compared to patients with Rec+/HER2- disease, those with Rec-/HER2- had significantly poorer 5-year LRC (84.2% versus 58.3%, HR = 4.36, P < 0.001) and worse survivals including 5-year DMFS (63.0% versus 15.8%, HR = 4.28, P < 0.001), DFS (59.7% versus 13.6%, HR=3.92, P < 0.001), and OS (87.8% versus 22.3%, HR = 8.55, P < 0.001). Other factors associated with reduced LRC were no radical surgery and involved field irradiation alone, whereas factors associated with poor survivals included positive nodes at primary diagnosis and regional recurrence. CONCLUSIONS: Constructed biologic subtypes remained to be predictive of both disease control and survivals after salvage radiation for postmastectomy ILRR. Notably, Rec-/HER2- patients were demonstrated to be at high risk of locoregional failure and subsequent DM and tended to have worse survivals despite salvage therapies.