PMRT After Neoadjuvant Therapy in ypN0/pCR Breast Cancer: Do We Still Need It?

Background: Modern neoadjuvant systemic therapy yields high pCR rates—especially in HER2-positive and triple-negative disease—raising whether PMRT (and broader regional nodal irradiation, RNI) remains necessary when axillary nodes convert to ypN0. pCR is prognostic, yet historical PMRT data predate today’s regimens. Methods: Narrative synthesis emphasizing contemporary randomized and meta-analytic evidence; subgroup considerations (subtype, initial clinical stage), and toxicity/quality-of-life. Results: The phase III NRG/NSABP B-51/RTOG 1304 trial randomized patients who were cN+ at diagnosis and converted to ypN0 after neoadjuvant therapy to RNI vs no RNI (with breast/chest-wall irradiation per surgery type). At ~5 years, RNI did not improve invasive breast cancer recurrence-free interval or overall survival; absolute event rates were low in both arms. These peer-reviewed results (NEJM, June 2025) support omission of RNI in responders (including the mastectomy subgroup). NRG OncologyAdventHealth Recent meta-analyses in ypN0 populations show lower locoregional recurrence with PMRT in selected higher-risk groups (e.g., residual disease, LVI-positive) but no consistent survival advantage, underscoring heterogeneity and the need for prospective selection. Lippincott JournalsPMC Meanwhile, pCR rates with contemporary HER2-targeted regimens are frequently >50–60% (even higher in ER-negative subsets), increasing the number of potential candidates for de-escalation. PMCASC Publications Conclusions: For patients initially cN+ who convert to ypN0, high-level evidence supports omitting RNI (and, by extension, avoiding PMRT solely for regional control) with excellent outcomes at 5 years. PMRT/RNI should be individualized for patients with residual disease, adverse biology, or other high-risk features. Longer follow-up and biology-integrated selection (e.g., ctDNA) are priorities