Abstract Background The prognosis and the value of postmastectomy radiotherapy (PMRT) between post‐chemotherapy ypT1‐2ypN1 and de novo pT1‐2N1 breast cancer (BC) remain controversial. We aimed to evaluate the prognostic differences and the effect of PMRT between the two patient subsets. Methods Patients diagnosed with pT1‐2N1M0 BC were identified between 2010 and 2018. The study endpoints were overall survival (OS), breast cancer‐specific survival (BCSS), locoregional recurrence‐free survival (LRFS), distant metastasis‐free survival (DMFS) and disease‐free survival (DFS). The chi‐square test, Kaplan–Meier method and Cox regression analysis were used for data analysis. Results Total number of 2103 pT1‐2N1M0 BC patients were included in the study, including 270 post‐chemotherapy (97 without PMRT, 173 with PMRT) and 1833 de novo cases (993 without PMRT, 840 with PMRT). No significant differences were found between post‐chemotherapy ypT1‐2ypN1 and de novo pT1‐2N1 BC patients in 5‐year OS (p = 0.068), BCSS (p = 0.054), LRFS (p = 0.241), DMFS (p = 0.104) or DFS (p = 0.08). PMRT did not improve any survival outcome in patients receiving neoadjuvant chemotherapy; however, the PMRT group had a better 5‐year BCSS (97.0% vs. 95.8%, p = 0.033) in de novo pT1‐2N1 BC. Cox multivariate analysis demonstrated that PMRT was a significant independent predictor of BCSS (HR 0.628; 95% CI, 0.403–0.978; p = 0.04) in de novo pT1‐2N1 patients. Conclusions There seemed no survival difference in post‐chemotherapy ypT1‐2ypN1 and de novo pT1‐2N1 BC patients with contemporary systemic therapy. In addition, PMRT might be exempted in patients with post‐chemotherapy ypT1‐2ypN1 BC, while not in patients with de novo pT1‐2N1 BC.
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