Evaluating the Association of Ki 67 with Oncotype DX Recurrence Score in Early-Stage ER Positive/HER2 Negative Breast Cancer

Background/Objectives Ki‑67 is widely used as an immunohistochemical marker of tumor proliferation in hormone receptor–positive (HR‑positive), HER2‑negative breast cancer, but its inter-pretation is limited by variability and uncertain concordance with genomic assays. The Oncotype DX® Recurrence Score (RS) is a validated multigene assay with established prognostic and predictive utility. This study evaluated the relationship between Ki‑67 and RS in clinical practice. Methods We retrospectively analyzed women in Greece with early‑stage estrogen receptor–positive, HER2‑negative breast cancer without distant metastasis (pM0) who under-went Oncotype DX testing between 2020 and 2023. Eligible patients were node nega-tive or postmenopausal with node positive disease. RS was categorized as low (0–25) or high (>25). Ki‑67 was assessed using binary (< 20% vs ≥20%) and three‑tier (≤5%, >5%–< 30%, ≥30%) classifications. Associations were analyzed using correlation, con-cordance, and nonparametric methods. Results Among 2,967 patients, the median RS was 16, with similar distributions across nodal subgroups. Ki‑67 and RS demonstrated a moderate positive correlation as continuous variables (r = 0.42, p <  0.001). After stratification, associations with RS were observed only in tumors with high Ki‑67 expression, whereas no correlation was detected in low or intermediate groups. RS distributions differed significantly across Ki‑67 strata. Overall concordance between Ki‑67‑based proliferation categories and RS‑based ge-nomic risk was 56.2%, with discordant cases in both directions. Conclusions Ki‑67 shows a moderate association with Oncotype DX RS, but substantial discordance indicates it should not substitute genomic testing in HR‑positive/HER2‑negative early breast cancer.