Efficacy of endocrine therapy alone versus endocrine therapy combined with radiotherapy after breast-conserving surgery in older patients with early-stage estrogen receptor-positive breast cancer: a meta-analysis

BACKGROUND: In the general adult female population, the benefit of adjuvant radiotherapy following breast-conserving surgery (BCS) is well established. Nevertheless, whether radiotherapy should be routinely added after BCS for older women with estrogen receptor-positive (ER+) breast cancer remains controversial. The present meta-analysis aimed to evaluate the efficacy and clinical value of endocrine therapy (ET) plus radiotherapy relative to ET alone in this population. METHODS: A systematic search was conducted across the Cochrane Library, PubMed, Embase, and Web of Science. Studies comparing ET plus radiotherapy versus ET alone in older (≥ 60 years) women with ER+ breast cancer after BCS were eligible. The primary conclusions were drawn exclusively on randomized controlled trials (RCTs), with findings from cohort studies serving as supporting evidence. Methodological quality was evaluated utilizing the National Institutes of Health Quality Assessment Tools. The meta-analysis was conducted in STATA (v15.0). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. Appropriate models were chosen for pooling results depending on between-study heterogeneity. Leave-one-out sensitivity analyses were performed to evaluate the robustness of findings. Outcomes comprised breast cancer-specific survival (BCSS), overall survival (OS), distant metastasis rate (DMR), local recurrence rate (LRR), and 5-year disease-free survival (DFS). Subgroup analyses were conducted by age, geographic region, ET regimen, radiotherapy regimen, and nodal status. For LRR, the absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. RESULTS: Twenty studies (9 RCTs, 11 cohort studies) met the eligibility criteria. The primary analysis based on RCTs revealed that radiotherapy plus ET reduced the risk of local recurrence (HR = 0.33, 95% CI: 0.18-0.60); the corresponding ARR was 3.2%, and NNT was 31. No statistically significant differences were observed between the two groups in OS (HR = 1.00, 95% CI: 0.89-1.13), BCSS (HR = 0.96, 95% CI: 0.48-1.93), DMR (HR = 1.12, 95% CI: 0.67-1.87), or 5-year DFS (HR = 0.64, 95% CI: 0.35-1.16). The results from cohort studies were reported separately as supporting evidence. CONCLUSION: For older women with early-stage ER+ breast cancer after BCS, adjuvant radiotherapy combined with ET reduces the risk of local recurrence, yet this combination demonstrates no statistically significant improvement in OS, BCSS, DMR, or 5-year DFS. The absolute benefit of radiotherapy is modest. Treatment decisions should involve individualized trade-offs incorporating the risk of recurrence, burden of comorbidities, life expectancy, and patient preferences.