Pathological complete response and postmastectomy radiation therapy after primary systemic therapy: results from the ReSTORE study

Background The ReSTORE study aimed to evaluate oncological outcomes and explore the association between pathological complete response (pCR), postmastectomy radiotherapy and nodal irradiation (PMRT), and recurrence. Methods This multicentre retrospective study included patients with breast cancer treated with chemotherapy-based primary systemic therapy (PST) followed by skin-or nipple-sparing mastectomy and immediate reconstruction. Locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) were analysed. Results A total of 256 patients were analysed, with a median follow-up of 82 months (range 16-166). In multivariable analysis, node-positive disease at diagnosis was associated with worse LRRFS (HR 8.28, 95% CI 1.06–64.34; p=0.043). PMRT was associated with a non-significant reduction in locoregional recurrence (HR 0.74, 95% CI 0.29–1.92; p=0.54). pCR was significantly associated with improved DFS (HR 0.48, 95% CI 0.28–0.82; p=0.008). Among patients receiving PMRT, those achieving pCR had superior DFS compared with those without pCR (HR 0.23, 95% CI 0.09–0.60; p=0.002). No significant associations with DFS were observed for age, BRCA status, tumour stage, or receptor status. Conclusions In this cohort, pCR and baseline nodal status were key prognostic factors, whereas the true impact of PMRT on outcomes remained uncertain. Nonetheless, our findings do not support omission of PMRT based on pCR alone. Prospective trials and long follow up are required to define response-adapted locoregional treatment strategies.