Re-evaluating the Role of Regional Nodal Irradiation for Node‐Negative Breast Cancer in the Modern Therapy Era: A Matched Cohort Analysis of EORTC 22922/10925

Background: While early breast cancer patients with node-negative disease generally exhibit a favorable prognosis and do not routinely require regional nodal irradiation (RNI), the EORTC 22922/10925 trial demonstrated that comprehensive nodal irradiation could potentially improve survival in selected N0 patients. To further investigate this paradigm, we applied the EORTC 22922/10925 trial criteria to a contemporary cohort of node-negative patients and evaluated their long-term outcomes. Methods: We retrospectively analyzed 2567 consecutive female patients with pT1–3N0 breast cancer who underwent curative surgery between January 2005 and December 2014. Among these, 1302 patients met the eligibility criteria of the EORTC 22922/10925 trial. Clinicopathologic characteristics, treatment details, and follow-up data were systematically collected. Primary endpoints included disease-free survival (DFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), locoregional recurrence–free survival (LRRFS), distant metastasis–free survival (DMFS), breast cancer recurrence–free survival (BCRFS), overall survival (OS), and breast cancer–specific survival (BCSS). Results: The EORTC-matched cohort demonstrated high 8.3-year survival: LRRFS 96.4%, DMFS 93.6%, DFS 90.0%, and OS 95.2%. In the overall cohort, non-RNI patients achieved 97.1% 8.3-year and 96.7% 10-year LRRFS. Multivariate analysis confirmed age ≤ 40 years and tumor size > 2.5 cm as independent LRRFS risk factors (both P < 0.05). Although high-risk patients (1–2 factors) had significantly lower LRRFS than low-risk patients (0 factors), their absolute outcomes remained favorable (95.0% at 8.3 years and 94.4% at 10 years). Conclusion: Patients with pT1–3N0 breast cancer receiving modern systemic therapy have excellent survival and low locoregional recurrence rates, both in the EORTC 22922/10925-matched cohort and overall. Despite higher risks associated with young age and larger tumors, absolute recurrence rates remain low, suggesting that routine RNI can be safely omitted in these patients.