Background: The role of postmastectomy radiotherapy (PMRT) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is controversial. We aimed to evaluate the effectiveness of radiotherapy in patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. Methods: We enrolled patients who received NAC and mastectomy for cT1–4 cN0–2 M0 breast cancer. We evaluated the association between radiotherapy and outcomes, locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) based on ypN status by multivariable analysis. Results: Of the 145,530 patients, we identified 3226 who met the inclusion criteria. Among ypN1 patients, no differences were found in LRR, DDFS, or OS between groups with and without radiotherapy (p = 0.72, p = 0.29, and p = 0.36, respectively). Radiotherapy was associated with improved LRR-free survival (p < 0.001), DDFS (p = 0.01), and OS (p < 0.001) in patients with ypN2–3. Multivariable analysis demonstrated that use of radiotherapy was independently associated with improved LRR [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.45–0.82, p = 0.001] and OS [HR 0.69, 95% CI 0.53–0.89, p = 0.004) for ypN2–3 patients only. The association between radiotherapy and OS was not statistically significant among ypN0 (p = 0.22) and ypN1 patients (p = 0.51). Conclusions: The results from this nationwide database study did not show significant associations between PMRT and improved survival among ypN0 and ypN1 patients. Radiotherapy may be beneficial only for ypN2–3 breast cancer patients who receive NAC and mastectomy in the modern era.
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