e12506 Background: Breast cancer accounts for a million new cases annually worldwide with 40,000 deaths reported in 2020 in the United States. Treatment includes surgery, adjuvant chemotherapy, radiotherapy and endocrine therapy. Oncotype recurrence score (RS), a 21-gene expression assay, is a tool to predict the benefit of adjuvant chemotherapy in hormone receptor (HR) positive breast cancer. High RS suggests benefit with chemotherapy. The goal of this study is to evaluate the relationship of the Oncotype RS with traditional prognostic/predictive factors. Methods: Retrospective IRB approved study of all patients from January 1, 2017, to December 31, 2019 with invasive breast cancer and an Oncotype RS in a community hospital setting. Study parameters included patient age, grade, tumor size, histologic subtype, HR status, number positive (0-4) lymph nodes (LN), extra nodal extension (ENE), lymphovascular invasion (LVI), and RS. Statistical analysis was done using linear regression and one-way ANOVA followed up with Tukey’s procedure. Results: A total of 470 patient charts evaluated and 22 patients excluded due to incomplete data with the following breakdown. LN positive = 14% (61/450). Oncotype score low (RS < 11) = 25% (114/448), intermediate (RS 11-25) = 59% (265/448) and high (RS > 25) = 15% (69/448). Grade 1 = 34% (153/448), Grade 2 = 50% (225/448) and Grade 3 = 15% (70/448). There was statistical significance in the mean difference in RS between the levels of grade and the levels of HR. The mean differences in RS between Grades 3 versus 1 was 10.9 (p < 0.001); between Grades 3 versus 2 was 8.3 (p < 0.001); and between Grades 2 versus 1 was 2.6 (p = 0.026). The mean Oncotype RS for grades 1,2,3 was 13.87 vs 16.33 vs 28.24 respectively. HR status was categorized as 51-100% (strong HR+), 11-50% (intermediate), or 1-10% (weak). Comparing strong HR+ versus intermediate/weak, the mean differences in RS were -41.4 and -35.7, respectively (p < 0.001). There were no significant differences in RS evaluated against the following parameters, patient age, tumor size, number of positive lymph nodes (0-4), LVI, or ENE. Conclusions: Tumor grade and HR status had strong association with the Oncotype RS as expected. Grade 3 tumor associated with high RS (mean 28). Intermediate HR (11-50%) associated with much higher RS = 52 similar to weak HR (1-10%) = 58. We report that RS had no correlation to patient age, tumor size or even LN status. The LN and RS association may have been impacted by low (14%) LN positive status (reportable in the modern era). Our study adds to the data that biology trumps size (traditional risk factors) while posing the question does intermediate HR status (11-50%) deserve recognition as a more substantial risk factor than previously considered.