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Purpose: The Oncotype DX© 21-gene Recurrence Score (RS) estimates the risk of distant disease recurrence in early-stage estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2- ) breast cancer. Using RS to estimate risk of locoregional recurrence (LRR) is less conclusive. We aimed to perform network meta-analysis (NMA) evaluating the RS in estimating LRR in ER+/HER2- breast cancer., Methods: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny., Results: 16 studies with 21,037 patients were included (mean age: 55.1 years (range: 22-96)). The mean RS was 17.1 and mean follow-up was 66.4 months. Using traditional RS cut-offs, 49.7% of patients had RS < 18 (3944/7935), 33.8% had RS 18-30 (2680/7935), and 16.5% had RS > 30 (1311/7935). Patients with RS 18-30 (risk ratio (RR): 1.76, 95% confidence interval (CI): 1.32-2.37) and RS > 30 (RR: 3.45, 95% CI: 2.63-4.53) were significantly more likely to experience LRR than those with RS < 18. Using TAILORx cut-offs, 16.2% of patients had RS < 11 (1974/12,208), 65.8% had RS 11-25 (8036/12,208), and 18.0% with RS > 30 (2198/12,208). LRR rates were similar for patients with RS 11-25 (RR: 1.120, 95% CI: 0.520-2.410); however, those with RS > 25 had an increased risk of LRR (RR: 2.490, 95% CI: 0.680-9.390) compared to those with RS < 11. There was a stepwise increase in LRR rates when applying traditional and TAILORx cut-offs (both P < 0.050)., Conclusion: RS testing accurately estimates LRR risk for patients being treated for early-stage ER+/HER2- breast cancer. Future prospective, randomized studies may validate the predictive value of RS in estimating LRR., (© 2022. The Author(s).)