Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor-positive breast cancer: a systematic review and network meta-analysis

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-022-06580-w.