Impact of Oncotype DX Risk Categorization and Receipt of Chemotherapy on Survival Outcomes Among Patients with Small Node-Negative HR+ Breast Cancer

BACKGROUND: The application of genomic assays, like Oncotype DX, for patients with small (T1mi/a/b) clinically node-negative (N0-N1mi) hormone receptor positive breast cancer (HR+BC) is becoming increasingly popular in real-world clinical practice. Whether these results can be reliably prognostic among this clinically low-risk population and can be used to make decisions on the application of adjuvant chemotherapy remains unknown. PATIENTS AND METHODS: Data from the National Cancer Database (NCDB) was examined for those diagnosed with small, node-negative HR+BC between 2010-2020. Oncotype DX recurrence score (RS) data was classified as low (RS < 11), intermediate (RS = 11-25), or high risk (RS = 26-100). Our primary objective was comparing overall survival (OS) based on chemotherapy receipt for those with high-risk scores. Kaplan-Meier methods and multivariable Cox proportional hazard models were used. Propensity score matching was additionally performed. RESULTS: Of the 350,911 patients with T1mi/a/b N0/N0(i+)/N1mi HR+BC, 102,357 (29.2%) had undergone Oncotype DX testing with available RS data available. Among them, 32,158 (31.4%) were low, 58,891 (57.5%) were intermediate, and 11,308 (11.0%) were high-risk. Chemotherapy receipt was documented in 1.2% (n=402) of low-risk, 6.8% (n=4000) of intermediate-risk, and 66.3% (n = 7496) of high-risk patients. Among high-risk patients, those who received chemotherapy have a lower risk of death compared to those in the chemotherapy omission arm, both on univariate (HR 0.55, 95%CI 0.52-0.72, P < 0.001) and multivariable (HR 0.61, 95%CI 0.52-0.72, P < 0.001) analyses. This finding remained true following propensity score matching (univariate HR 0.63 95%CI 0.52-0.76; aHR 0.71 95%CI 0.59-0.86; P < 0.001 for both). Factors associated with high RS included higher tumor grade, Black race, and lymphovascular invasion. CONCLUSION: Our findings suggest that risk stratification through a genomic assay such as Oncotype DX may be advantageous, even among otherwise clinically low-risk individuals with HR+BC.