Role of Adjuvant Radiotherapy in Clinically Node-Positive Breast Cancer With Pathologic Nodal Complete Response After Neoadjuvant Chemotherapy: A Review

Roham Salek; Seyedehhoda Khatibmasjedi; Seyed Alireza Javadinia

doi:10.31557/RRO.2025.11.1.153

Authors

Roham Salek Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Seyedehhoda Khatibmasjedi Palliative care department, Case Western Reserve University, University Hospitals, Seidman Cancer Center, Cleveland, Ohio, USA.
Seyed Alireza Javadinia Associate Professor, Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.

DOI:

https://doi.org/10.31557/RRO.2025.11.1.153

Abstract

Background: Neoadjuvant chemotherapy (NAC) can eradicate axillary disease in patients with initially node-positive breast cancer, resulting in pathologic node-negative status (ypN0). The role of postoperative radiotherapy (RT), particularly regional nodal irradiation (RNI), in this setting remains uncertain. This review summarizes current evidence on adjuvant RT after nodal pathologic complete response to NAC.

Materials and Methods: Recent clinical trials, prospective studies, retrospective cohorts, registries, and meta-analyses evaluating adjuvant RT in initially node-positive breast cancer achieving ypN0 status after NAC were reviewed and synthesized.

Results: The phase III NSABP B-51/RTOG 1304 trial included 1,556 patients with cT1–3N1 breast cancer who achieved nodal pCR after NAC. At 5 years, RNI did not significantly improve invasive breast cancer recurrence-free interval compared with no RNI (approximately 92% in both groups; HR=0.88, 95% CI: 0.60–1.28; P=0.51). Retrospective meta-analyses suggest that locoregional RT reduces locoregional recurrence but has not demonstrated a clear disease-free or overall survival benefit. The RAPCHEM registry also reported low 5-year locoregional recurrence rates with response adapted RT in selected low-risk ypN0 patients. However, retrospective registry data suggest that patients with high-risk features, including triple-negative disease or more advanced initial stage, may derive greater benefit from locoregional irradiation.

Conclusions: Current evidence supports selective de-escalation of postoperative nodal RT in carefully selected patients with initially node-positive breast cancer who achieve ypN0 status after NAC. However, RT decisions should remain individualized according to initial clinical stage, tumor biology, treatment response, and other risk factors. Further prospective evidence is needed to define which patients can safely avoid comprehensive locoregional irradiation.