Individualized risk stratification for postmastectomy radiation therapy in node-positive breast cancer: moving beyond universal guidelines

Postmastectomy radiation Therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality in patients with ≥4 positive lymph nodes. However, evidence supporting PMRT in patients with 1-3 positive nodes remains limited. While the 2014 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis demonstrated benefit in this population, the constituent trials preceded current standard practices including sentinel lymph node biopsy, contemporary systemic therapies, and modern radiation therapy techniques. This analysis examines the applicability of EBCTCG findings to current clinical practice. Historical trials reported elevated LRR rates, potentially attributable to inadequate axillary staging and suboptimal systemic therapy regimens such as cyclophosphamide, methotrexate, and fluorouracil. Contemporary studies demonstrate substantially lower LRR rates in comparable patients managed without PMRT, particularly those with favorable tumor characteristics. Current adjuvant therapies-including anthracyclines, taxanes, trastuzumab, endocrine agents, and targeted therapies such as abemaciclib and olaparib-have markedly reduced recurrence risk. Retrospective analyses yield conflicting results regarding PMRT efficacy, while randomized trials (SUPREMO, TAILOR RT) seek to refine treatment indications. Contemporary practice should not universally recommend PMRT for intermediate-risk patients (1-3 nodes); instead, individualized risk assessment is warranted. The role of PMRT remains undefined in patients without axillary lymph node dissection or those achieving pathologic complete response following neoadjuvant therapy. Clinical decision-making must consider treatment benefits relative to potential late toxicities and reconstructive complications. Personalized, evidence-based approaches informed by emerging trial data represent the optimal strategy for patient management.