Abstract P4-12-01: Correlation between the Oncotype DX Recurrence Score® categories and progression-free survival of patients with primary metastatic estrogen-receptor positive and HER2-negative breast cancer

Abstract Background: The Oncotype DX Recurrence Score® assay is a 21-gene biomarker validated to provide individualized prognostic estimates of distant recurrence risk and predictive information on the benefit of chemotherapy in patients with early-stage, ER+, HER2- BC. In ER-positive, HER2-negative primary metastatic BC (PMBC), endocrine therapy (ET) is the preferred option for first-line therapy, unless there is a high visceral burden of disease in which case chemotherapy (CT) alone or chemoendocrine therapy (CET) may be considered. There are many unanswered questions related to the optimal management of endocrine responsive PBMC, including optimal drug sequencing, and the potential for individualized treatment on the basis of predictive markers. Studies are warranted to understand individualized treatment response based on PMBC tumor biology and treatment naivety. The primary objective of this retrospective study is to evaluate the association of the Recurrence Score® (RS) result with progression-free survival (PFS) in a cohort of German patients with ER+, HER2- PMBC who received treatment independent of the RS result. Methods: Patients diagnosed with ER+/HER2- PMBC between 2008 and 2018 were included in this retrospective analysis. The RS result was collected retrospectively and as such was not used for clinical decision-making. Descriptive analyses were used to characterize patient and tumor characteristics. T-tests and Wilcoxon rank sum tests were used to compare continuous characteristics between RS result groups (0-25 and 26-100). Chi-square and Fisher’s exact tests were used to compare categorical characteristics between RS result groups. Kaplan-Meier estimates and log-rank tests were used to compare PFS and 2-year overall survival (OS) between RS result groups. Multivariable Cox regression models adjusted for age, grade, treatment, and RS result were used to examine the association between RS result with PFS and OS. Results: A total of 75 patients were included in this analysis (47 had a RS result of 0-25 and 28 had a RS result of 26-100). Mean (SD) age differed between RS groups (p = 0.03); 69.3 (12.6) years for RS 0-25 and 60.1 (17.4) years for RS 26-100. First-line systemic therapy also differed between RS groups (p = 0.004); for patients with RS results 0-25, 38 (80.9%) received ET, 5 (10.6%) received CET, and 3 (6.4%) received (CT). For RS results 26-100, 13 (46.4%) patients received ET, 11 (39.3%) received CET, and 4 (14.3%) received CT. For RS results 0-25, patients were older, post-menopausal, and had less CT assigned as treatment. The RS result 26-100 cohort consisted of younger, more pre-menopausal women, with a greater percentage assigned CT alone or CET. The RS 0-25 group had significantly improved PFS (p=0.013) with a median of 35 months compared to 12 months in the RS 26-100 group. The difference in 2-year overall survival rates between the RS 0-25 group (79%) vs. RS 26-100 group (63%) did not reach statistical signifiance (p=0.18). In multivariable Cox regression models, the RS result was prognostic for PFS and 2-year OS (p=0.002 and 0.010, respectively). Conclusions: In this retrospective analysis, there were differences in treatment assignments based on clinical risk of PMBC that were consistent with treatment recommendations according to RS outcomes in EBC. The binary RS result cut offs (RS ≤25; RS >25) were prognostic for PFS and OS in this retrospective analysis of patients with ER+/HER2- PMBC. These findings suggest that the Oncotype DX® assay also reflects tumor biology in PMBC, and genomic assays standardly used in early breast cancer might warrant further prospective investigation in the treatment-naïve advanced setting. Citation Format: Marc Thill, Raissa Shvartser, Paige Innis, Purva Singla, Satish Seerapu, Katrin Ehlert. Correlation between the Oncotype DX Recurrence Score® categories and progression-free survival of patients with primary metastatic estrogen-receptor positive and HER2-negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-01.