Abstract P6-01-24: Long-term outcome data using Endopredict® as risk stratification and chemotherapy decision biomarker in hormone receptor positive, HER2-negative early breast cancer
Authors: Klein Evelyn , Josipovic Adriana , Noske Aurelia , Anders Sophie , Mogler Carolin , Weichert Wilko , Hapfelmeier Alexander , Kiechle Marion , Ettl Johannes 
Published: March 2023

Abstract
Background: The Endopredict test is used for estimating risk of distant recurrence for women presenting with early-stage breast cancer with a positive estrogen receptor (ER) and negative human epidermal growth factor receptor 2 (HER2) status. The current ASCO Guideline Update on biomarkers confirms the value of the Endopredict test to guide decisions of adjuvant endocrine and chemotherapy. This study shows prospective long-term outcome data of early breast cancer patients whose chemotherapy decision was guided by the Endopredict test result (EPclin). Methods: ER-positive and HER2-negative early breast cancer patients with 0-3 positive lymph nodes treated between March 2012 and March 2015 were included in this single institution study. The Endopredict® test was carried out on all tumour samples. Demographic, clinical and pathological data were assessed for each patient at baseline. Treatment compliance, local recurrence, distant metastases and survival was evaluated. Risk estimates were obtained by the Kaplan-Meier method and cumulative risk functions in case of competing risks. Group comparisons were performed by Cox proportional hazards regression models and quantified through hazard ratios. Median Follow-Up was estimated by the inverse Kaplan-Meier method. Exploratory hypothesis testing was conducted at two-sided 5% significance levels. Results: In a cohort of 368 consecutive cases the median follow-up time was 8.2 years. Endopredict allocated 238 pts (64%) in the EPclin low risk and 130 pts (34%) in the EPclin high risk group. The 5-year distant metastasis free survival (DMFS) in the EPclin low risk group was 96.6% (95% CI 0.943-0.989) and 85.5% (95% CI 0.796-0.920) in the EPclin high risk group. With a hazard ratio (HR) of 2.21 (95% CI: 1.27-3.88; p=0.005) the risk for distant metastasis in EPclin high risk patients was more than two-fold higher in comparison with EPclin low risk patients. 87 pts. (66.9%) of the EPclin high risk group underwent chemotherapy (compliant), whereas 43 pts (33.1 %) opposed the recommended chemotherapy (non-compliant). Kaplan-Meier plots in the EPclin high risk subgroups compliant vs non-compliant showed a significant disease-free survival (DFS) benefit towards the patients following the chemotherapy recommendation (HR 0.46; 95%CI 0.23-0.95; p=0.036). The 5-year DFS for the high risk compliant subgroup was 89.1% (95% CI: 0.827-0.961) vs. the high risk non-compliant subgroup with 68.9% (95% CI: 0.562-0.845). Regarding the subgroups pre- and postmenopausal, patients with a EPclin high risk test result were at significant higher risk of experiencing distant metastases than patients with a EPclin low risk test result in both subgroups (premenopausal: HR 3.55; 95%CI 1.17-12.32; p=0.025; postmenopausal: HR 1.19; 95%CI 0.99-3.7; p=0.054). We analyzed the EPclin categorization in context of the ki67 subtypes luminal A (low; 0-10%) and luminal B (high; 25-100%). The EPclin-based risk stratification was significantly associated with improved DFS in both ki67 subtypes (ki67 low: HR 4; 95%CI 1.25-12.04; p=0.021 and ki67 high: HR 3.77; 95%CI 1.19-18.93; p=0.022). 33.3% (21 pts) of all tumor samples classified as luminal B (63 pts), were reclassified towards the low risk group via Endopredict, sparing chemotherapy recommendation. Contrary 19.2% (14 pts) of all luminal A (73 pts) were categorized to high risk EPclin. Conclusion: These first long term prospective outcome data confirm, that Endopredict can guide decisions on adjuvant chemotherapy in early ER positive, HER2 negative breast cancer. Pts categorized as EPclin high risk benefitted from an adjuvant chemotherapy. Our results show that Endopredict risk stratification is also applicable in premenopausal women. Furthermore the Endopredict test showed a better classification accuracy in comparison to ki67 subtypes, resulting in a more precise estimation of prognosis.
Citation Format: Evelyn Klein, Adriana Josipovic, Aurelia Noske, Sophie Anders, Carolin Mogler, Wilko Weichert, Alexander Hapfelmeier, Marion Kiechle, Johannes Ettl. Long-term outcome data using Endopredict® as risk stratification and chemotherapy decision biomarker in hormone receptor positive, HER2-negative early breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-24.