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ObjectiveTo compare long-term survival in early-stage breast cancer patients treated with different radiation therapy modalities.MethodsData was retrospectively derived from SEER database. We compared overall survival (OS), breast cancer specific survival (BCSS) and second primary malignancies (SPM) in early-stage breast cancer patients treated with postoperative radiotherapy (PORT) versus those treated neoadjuvant radiotherapy (NART) and intraoperative radiotherapy (IORT) after propensity score matching by 1:1.ResultsA total of 457,166 patients were included in this study. After matching, the 20-year OS of 1441 patients in NART cohort was lower than that in PORT cohort (p < 0.01), particularly in hormone receptor positive patients (p < 0.01). NART were dependent prognostic factors for 20-year OS [Hazard Ratio (HR):1.21, 95%CI: 1.06-1.38, p < 0.01). No significant difference in BCSS was observed between NART and PORT treatments. Additionally, patients undergoing NART had a lower risk of all SPM (p = 0.01) and second solid cancers (p = 0.02) but a comparable risk of second hematological malignancies (p = 0.55) than patients administered PORT. HR-positive was a risk factor for SPM. No OS, BCSS or SPM risk difference were significantly observed in the 2096 pairs of IORT and PORT groups.ConclusionCompared to PORT, NART and IORT don't offer survival advantages for early-stage breast cancer patients. Altering the sequence of radiotherapy requires careful evaluation.