De-escalating locoregional radiation therapy in breast cancer: balancing promises and prudence

Introduction: The integration of primary systemic therapy (PST) into breast cancer management increasingly shapes locoregional treatment. Rising pathological complete response rates and improved survival have fueled interest in radiation therapy (RT) de-escalation to limit late toxicity while preserving oncological control. Yet the risk of undertreatment and its delayed consequences remains a major concern. Areas covered: This article appraises evidence supporting response-adapted RT de-escalation after PST. We review key prospective and retrospective studies, including RAPCHEM and NSABP/B-51, outlining their methodological strengths, limitations, and clinical relevance. Evidence was identified through a focused narrative review of major clinical trials, pooled analyses, and meta-analyses addressing locoregional management in the post-PST setting. We further discuss how contemporary systemic therapies, evolving surgery, molecular profiling, and technological advances in RT inform individualized decision-making. Expert opinion: Early data suggest that RT de-escalation may be feasible for carefully selected patients, but current evidence does not justify unrestricted omission of RT in all pathological complete responders. Decisions should remain grounded in long-term outcomes, accurate pre-treatment staging, and robust validation of predictive biomarkers. Until such evidence matures, RT de-escalation should be undertaken cautiously–preferably within clinical trials or prospective registries and following multidisciplinary review–to minimize the risk of inadvertent locoregional undertreatment.