Abstract PS3-08-11: Correlation between clinical-pathological features and recurrence score from a multigene predictive assay in hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer: a real-world, retrospective, monocentric analysis of over 700 patients

Abstract Background: Adjuvant cytotoxic chemotherapy followed by endocrine therapy, with or without cyclin dependent Kinase 4/6 (CDK4/6) inhibitors, significantly reduced the risk of tumor recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (eBC) and high-risk clinical-pathological features. Oncotype DX is a validated genomic assay that provides valuable prognostic information to identify patients with eBC who benefit from adjuvant chemotherapy. However, the association between Oncotype DX recurrence score (RS) and clinical-pathological features has not been fully clarified. Here we present a large real-world retrospective analysis of patients with HR+/HER2- eBC undergoing Oncotype DX test at IRCCS Istituto Nazionale dei Tumori. Methods: We conducted a monocentric, retrospective study to investigate the association between Oncotype DX and clinical-pathological features in HR+/HER2− eBC between patients who underwent breast surgery between June 2009 and December 2024. Patients were divided into three risk groups according to RS: low (≤10), intermediate (11-25), and high (≥26). The association between clinical-pathological features and categorized RS was reported as odds ratio (OR). A multivariable cumulative link model was fitted to adjust the associations for ten clinically relevant covariates in both the overall population and the subgroups of patients with (N+) or without (N0) lymph node involvement. Results: Among 732 patients included in the study, Oncotype DX identified 149 (20.3%) patients as low genomic risk, 443 (60.5%) as intermediate risk, and 140 (19.2%) as high risk. After multivariable adjustment, lower progesterone receptor (PgR) expression and higher Ki67 levels were independently associated with a higher RS, whereas lobular histology and older age were associated with lower RS (Table). PgR and Ki67 expression were also significantly associated with RS in both N0 and N+ subgroups (Table). Lobular histology and older age were significantly associated with lower RS only in N0 and N+ patients, respectively (Table). Conclusions: Among clinical-pathological features, Ki67 and PgR showed the most consistent association with genomic risk. In case of limited access to genomic testing, PgR and Ki67 may represent the most reliable markers for prognostic and predictive stratification, alongside lobular histology in N0 tumors and age in N+ cases. Citation Format: G. Mazzoli, G. Fotia, M. De Santis, A. Fumagalli, G. Armani, L. Lozza, D. Presti, R. Agresti, M. Gennaro, C. Volpi, C. Vernieri, S. Folli, G. Pruneri, G. Scaperrotta, F. De Braud, G. Capri, G. Bianchi. Correlation between clinical-pathological features and recurrence score from a multigene predictive assay in hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer: a real-world, retrospective, monocentric analysis of over 700 patients abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-11.