Clinical Impact and Clinicopathologic Correlations of Oncotype DX in Hormone Receptor-Positive/HER2-Negative Early Breast Cancer: Real-World Evidence From a Large Brazilian Cohort (GBECAM 0520).

Abstract

Oncotype DX (ODX) is a validated gene expression assay that provides prognostic and predictive information to guide adjuvant chemotherapy (ACT) decisions in hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (eBC), including node-negative (N0) and 1-3 node-positive (N1) disease. In Brazil, limited access to gene expression signatures (GES) remains a barrier to individualized treatment decisions. We conducted a multicenter retrospective study across nine Brazilian private cancer centers to evaluate clinicopathologic predictors of high genomic risk (ODX recurrence score [RS] >25) and to assess the clinical impact of ODX on ACT decision making. Between 2005 and 2024, 935 patients were included, with a notably higher representation of young (≤40 years: 10.9%) and premenopausal (40.7%) women than typically reported in randomized clinical trials. Ki-67 >20%, progesterone receptor (PR) expression ≤30%, and histologic grade 3 were independently associated with high RS in both univariable and multivariable analyses (all <i>P</i> <.001), with Ki-67 emerging as the strongest clinicopathologic predictor. Overall, ODX testing was associated with an estimated 12.6% absolute reduction in ACT recommendations, with substantial impact among postmenopausal patients with N1 disease (94% absolute reduction) and N0 patients older than 50 years with high clinical risk (65.2% absolute reduction). With a median follow-up of 4.8 years, the estimated 5-year real-world invasive disease-free survival and distant disease-free survival were 100% and 100% for those with RS <11, 98.2% and 99.4% for RS 11-25, and 90.9% and 92.5% for RS >25, respectively. In this data set, ODX demonstrated utility in guiding ACT decision making and supporting personalized treatment by reducing both overtreatment and undertreatment. In resource-constrained settings, surrogate markers such as Ki-67, PR expression, and histologic grade may serve as practical tools to guide risk-adapted clinical decisions.