Radiation Management After Neoadjuvant Therapy in Breast Cancer: Current Evidence and Evolving Paradigms

Purpose of Review Neoadjuvant chemotherapy (NAC) has become an integral component of modern breast cancer management, particularly for patients with triple-negative and HER2-positive disease. As pathologic complete response (pCR) rates improve with current systemic therapies, the optimal role of adjuvant radiotherapy (RT) after NAC has become an area of active investigation. This review summarizes current evidence, evolving guidelines, and ongoing clinical trials evaluating RT de-escalation and treatment personalization after NAC. Recent Findings Response to NAC is strongly associated with clinical outcomes and increasingly informs locoregional treatment decisions. The phase III NSABP B-51/RTOG 1304 trial demonstrated low recurrence rates and no significant benefit at 5 years from regional nodal irradiation (RNI) in patients with cT1-3N1 disease who achieved ypN0 status after NAC, findings now incorporated into updated NCCN and ASTRO-ASCO-SSO guideline recommendations. Additional studies, including RAPCHEM and retrospective analyses, support selective de-escalation of RNI in carefully selected patients, while ongoing trials continue to evaluate omission of whole-breast irradiation (WBI) and optimization of axillary management. Emerging data also highlight the increasing complexity of integrating RT with modern adjuvant systemic therapies, including immunotherapy, HER2-targeted agents, CDK4/6 inhibitors, and PARP inhibitors. Summary Advances in systemic therapy and improved response assessment are driving a transition toward more individualized, response-adapted RT strategies after NAC. Ongoing trials, including Alliance A011202, ADARNAT, ATNEC, DESCARTES, and ROSALIE, will further define the optimal integration, sequencing, and de-escalation of RT in the post-NAC setting.