Background: The EndoPredict test is a clinico-molecular test that has been validated to predict the likelihood of distant metastases and late relapse inpatients (pts) with hormone receptor positive (HR+), HER2-negative (HER2-) early breast cancer and up to three positive lymph nodes. However, so far prospective outcome results of pts in whom decision on use of adjuvant chemotherapy (CTX) was based on Endopredict has not been available. Here we present three year outcome data of pts, whose adjuvant systemic therapy recommendation was based on EndoPredict test result.

Methods: Pts with HR+, HER2- early breast cancer with 0-3 positive lymph nodes were enrolled at a single institution (Interdisciplinary Breast Center of Klinikum rechts der Isar, Munich, Germany). The Endopredict test was carried out on all tumor samples. Demographic, clinical and pathological data as well as EPclin risk class were assessed for each patient at baseline. Therapy recommendations were given during an interdisciplinary tumor board. Pts were evaluated for treatment compliance, local recurrence, distant metastases and survival (cut-off date of last follow up: July 31st 2017). Censored time-to-event outcomes were analysed by cox proportional hazards models. Additional estimates of the event-free-survival were given by the Kaplan-Meier method. Hypothesis testing was conducted on two-sided exploratory 5% significance levels.

Results: A total of 373 consecutive pts were enrolled between March 2012 and March 2015. Median age was 59.9 (range: 29.1-88.9) years. In 39% of pts tumorsize was >2cm, 24% of pts were node positive, 16% had G3 tumors, in 21% of pts ki67 was ≥25% and in 13% progesterone receptor was <10%. The EndoPredict test allocated 238 pts (63.8%) in the low-risk group and 135 pts (36.2%) in the high-risk group. 128 of the 373 pts were recommended to undergo adjuvant CTX in addition to endocrine therapy. 92 (72%) of these pts were compliant having received standard of care chemotherapy. After 41.6 months median follow up, 3-year disease free survival (DFS) and distant metastases free survival (DMFS) in the EPclin low risk group was 96.6% (95%CI 94.2-99.1) and 99.6% (95%CI 98.7-100) versus 94.9% (95%CI 90.9-99.0) and 97.6% (95%CI 95.0-100) in the EPclin high risk group. With a hazard ratio (HR) of 2.05 (95%CI 0.85-4.96; p= 0.110) risk for any disease recurrence or death in EPclin high risk patients was two fold higher in comparison with EPclin low risk patients. Patients with EPclin high risk were at significant higher risk of experiencing distant metastases than patients with EPclin low risk (HR 5.18; 95%CI 1.04-25.74; p=0.0443). EPclin high risk patients who actually underwent recommended adjuvant CTX had a 3-year-DFS of 96.3% (95%CI 92.2-100) and were at lower risk for death or recurrence than those EPclin high risk patients without CTX (3-year-DFS: 91.5% (95%CI 82.7-100); HR 0.32; 95%CI 0.10-1.05; p=0.061).

Conclusion: These first prospective outcome results show, that EPclin in clinical routine is a valid clinico-molecular marker to predict DFS and guide decision of adjuvant CTX use in HR+, HER2- early breast cancer pts with 0-3 positive lymph nodes.

Citation Format: Ettl J, Anders S, Hapfelmeier A, Noske A, Paepke S, Weichert W, Klein E, Kiechle M. First prospective outcome data for the clinico-molecular test Endopredict® in hormone receptor positive, HER2-negative early breast cancer in clinical routine [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-11.