Authors: Fatjona Kraja, Erald Karaulli, Athina Papallopullo, Edit Zaganjori, Florina Hoxha, Adrian Hoti
Published in AJMHS Vol 71, 2026 (Ahead of Print)
Keywords: radiotherapy, early breast cancer, guidelines
Background: Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) reduces ipsilateral breast tumor recurrence (IBTR), but the absolute benefit varies with baseline risk. With modern systemic therapy and molecular profiling, a subset of patients has sufficiently low local-recurrence risk to consider RT de-escalation or omission.
Methods: We analyzed evidence from randomized trials in older, hormone-receptor–positive (HR+) early breast cancer, prospective cohort studies and current guidelines. Key outcomes were IBTR, distant relapse, overall survival (OS), and toxicity/quality-of-life (QoL).
Results: Two randomized trials validate RT omission in elderly, low-risk HR+ disease receiving endocrine therapy. CALGB 9343 (age ≥70, T1N0, ER+) showed higher 10-year IBTR with omission (≈10% compared with 2% with RT) without OS difference. PRIME II trial (age ≥65, ER+, ≤3 cm, N0) confirmed as a 9–10% absolute increase in 10-year IBTR without OS loss. Biologically selected cohorts suggest omission can transcend age criteria. For women ≥55 years with luminal A tumors (ER+, HER2–, grade 1–2, Ki-67 ≤13.25%) who are treated with endocrine therapy alone in the LUMINA trial, 5-year locoregional recurrence was ~2–3% with great distant control without RT. On-going randomized trials as PRECISION and EXPERT are comparing genomic testing such as Oncotype DX, Prosigna/PAM50 to guide RT omission.
Randomized and prospective data support RT in most DCIS, yet small, low-grade, wide-margin screen-detected lesions of low risk could be suitable for surveillance or surgery alone. Active-surveillance trials are also underway on this topic. On the other hand, de-escalation alternatives like ultra-hypo fractionated whole-breast RT and partial-breast irradiation have local control with reduced burden of treatment.
Conclusions: RT omission is safe for carefully selected elderly patients with small, node-negative, ER+ tumors on endocrine therapy, with no OS penalty. Biology and genomics can further help in patients’ selection. Shared decision-making, adherence to endocrine therapy and multidisciplinary review are essential.
https://doi.org/10.65413/.........