Abstract P2-03-23: Retrospective evaluation of outcomes in a real-world, prospective cohort using EndoPredict: Results from the Charité registry
Authors: Schmitt Wolfgang D. , Jank Paul , Hoffmann Inga , Pfitzner Berit M. , Lenz Lauren , Clegg Wyatt , Keil Elke , Ratzel Sarah , Cogan Elizabeth S. , Blohmer Jens-Uwe , Wimberger Pauline , Kronenwett Ralf , Horst David , Denkert Carsten 
Published: March 2023

Abstract
Background: EndoPredict is a prognostic and predictive gene expression assay that provides an EPclin risk score, which can be used to identify individuals with low enough risk of distant breast cancer recurrence that they may forgo chemotherapy. In clinical studies, EndoPredict has been validated to predict risk of distant recurrence up to 15 years and chemotherapy benefit. To date, real-world studies evaluating patient outcomes after prospective EndoPredict testing have been limited. Here, we report on outcomes collected via survey from patients enrolled in a registry created to generate real-world evidence from over 800 patients routinely tested with EndoPredict at Charité University Hospital Berlin. Methods: Female patients with hormone receptor positive, HER2 negative primary breast cancer with up to three positive lymph nodes who received prospective EndoPredict testing at Charité University Hospital Institute of Pathology between 2011 and 2016 were contacted to complete a survey for participation in this study. Surveys included questions on treatment and recurrence history. Patient demographics, clinical characteristics of the cancer, and EndoPredict results were retrieved from Charité records. All patients received EndoPredict test results before decision making on systemic treatment. After testing, treatment included either adjuvant endocrine therapy or adjuvant endocrine therapy plus adjuvant chemotherapy, and may have included radiotherapy. Cox proportional hazards models were fit with binary EPclin risk category (high, low) or continuous EPclin risk score predicting 5-year distant recurrence or recurrence of any kind. Analyses were performed across all survey responses, and in subsets of patients stratified by adjuvant chemotherapy treatment. Kaplan-Meier estimates of 5-year risk of recurrence were also calculated. Results: 842 patient survey responses were returned with informed consent and met study inclusion criteria. The median age at diagnosis was 54 years (IQR 49, 63), and across survey responses, 63.5% (N=535/842) of patients were lymph node negative, 60.9% (N=513/842) were T1, and 43.9% (N=370/842) were treated with adjuvant chemotherapy. Among included patients, 49.5% (N=417/842) were classified as EPclin low-risk and 50.5% (N=425/842) were high-risk. The concordance between EPclin risk category and chemotherapy status was 0.89 with 5.5% (N=23/417) of EPclin low-risk and 81.6% (N=347/425) of EPclin high-risk patients receiving treatment with chemotherapy. In the subset of patients not treated with adjuvant chemotherapy (N=472/842, 55.7%), continuous EPclin score was a significant predictor of distant recurrence (N=469; HR: 4.34, 95% CI 1.75-9.58); p = 2.4 × 10-3), and recurrence of any kind (N=468; HR: 3.39, 95% CI 1.61-6.58); p = 1.9 × 10-3). In EPclin low-risk patients treated with endocrine therapy alone, there was a low risk of 5-year distant recurrence (1.6%, 95% CI 0.7%-3.4%). In EPclin high-risk patients the risk of distant recurrence at 5 years was 6.8% (95% CI 2.6%-17.4%) in patients without chemotherapy and 3.6% (95% CI 2.1%-6.3%) in patients treated with chemotherapy. In an exploratory subgroup analysis in patients with node negative and node positive disease, risk of 5-year distant recurrence in EPclin low-risk patients without chemotherapy was 1.3% (95% CI 0.5%-3.5%) and 2.4% (95% CI 0.6%-9.2%), respectively. Conclusion: In this real-world cohort of patients with prospective routine testing with EndoPredict, EPclin scores were a significant predictor for patient-reported outcomes. Patients with EPclin low-risk scores had a low risk of 5-year distant recurrence even in the absence of chemotherapy treatment. This real-world result supports previous clinical studies demonstrating that patients with EPclin low-risk scores can safely forgo chemotherapy.
Citation Format: Wolfgang D. Schmitt, Paul Jank, Inga Hoffmann, Berit M. Pfitzner, Lauren Lenz, Wyatt Clegg, Elke Keil, Sarah Ratzel, Elizabeth S. Cogan, Jens-Uwe Blohmer, Pauline Wimberger, Ralf Kronenwett, David Horst, Carsten Denkert. Retrospective evaluation of outcomes in a real-world, prospective cohort using EndoPredict: Results from the Charité registry [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 P2-03-23.