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Invasive disease-free survival (IDFS) rates are excellent in patients with breast cancer (BC) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), axillary lymph node-negative (LN-) tumors with a 21-gene expression assay recurrence score (RS) of 0 to 10. However, to the authors' knowledge, the outcomes among patients with an RS of 11 to 25 who are treated with endocrine therapy alone are unknown.In this retrospective single-institution study, the authors described the characteristics of patients with HR+, HER2-, LN- BC who underwent a 21-gene expression assay. In addition, among those individuals diagnosed between 2005 and 2011, we measured IDFS, recurrence-free survival, distant recurrence-free survival, and overall survival rates, focusing on patients with an RS of 11 to 25 by receipt of chemotherapy. The Kaplan-Meier method was used to estimate survival rates and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (95% CIs).Among 1424 patients, the RS distribution was 0 to 10 in 297 patients (21%), 11 to 25 in 894 patients (63%), and >25 in 233 patients (16%); of these, 1.7%, 15%, and 73.4% of patients, respectively, received chemotherapy. With a median follow-up of 58 months, those patients with an RS of 11 to 25 had an IDFS rate at 5 years of 92.6% (95% CI, 89.6%-94.7%), which was comparable between those who received chemotherapy and those who did not. The hazard ratios of the effect of chemotherapy were 1.64 for IDFS (95% CI, 0.73-3.71), 1.46 for recurrence-free survival (95% CI, 0.41-5.23), 1.25 for distant recurrence-free survival (95% CI, 0.32-4.92), and 2.19 for overall survival (95% CI, 0.44-11.0).The results of the current study demonstrate similar outcomes with or without chemotherapy in patients with HR+, HER2-, LN- BC who have an RS of 11 to 25, but a benefit from chemotherapy in this group cannot be ruled out.The current study demonstrates similar breast cancer-related outcomes with or without chemotherapy among patients with early-stage breast cancer with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative disease who have tumors with a 21-gene recurrence score of 11 to 25 and receive adjuvant endocrine therapy. However, due to a relatively short follow-up and small number of outcome events herein, the benefit of chemotherapy cannot be ruled out in this group of patients.