PurposeMultigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.Materials and MethodsWe retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.ResultsAmong 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).ConclusionOncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.