Adherence to EndoPredict test scores for extended endocrine therapy management in the prospective EndoPredict Extended Endocrine Trial (EXET).

537 Background: Current guidelines advise that individuals with estrogen receptor-positive (ER+) breast cancer (BC) undergo 5 years of endocrine therapy with consideration of up to 10 years of extended endocrine therapy (EET). The relative benefit of EET beyond 5 years is minimal for many patients, yet a significant group of patients at higher risk of late recurrence may benefit. EndoPredict is a gene expression assay to stratify those with high versus low BC recurrence risk and is validated to predict early and late distant metastasis up to 15 years using an EPclin score. In the prospective EXET study we evaluated adherence to EndoPredict test results when making decisions regarding EET. Methods: Patients with prior ER+, human epidermal growth factor 2 negative (HER2-) BC diagnosis and 4-6.5 years of endocrine therapy underwent EndoPredict testing. To evaluate the impact on decision making for EET, chart review was performed at or after test results were clinically disclosed. Univariable analysis was used for EPclin risk classification (high, low), multivariable analysis was used to evaluate the EPclin score with clinical variables and Firth logistic regression was used to assess the association of a given variable with the therapy decision. Results: The cohort consisted of 411 patients with an average age of 62 years (range 27, 90), 107 received adjuvant chemotherapy (26%), and 71 were lymph node positive (17.3%). The rate of EET was significantly different for those with low-risk scores (EPclin Score ≤ 3.3) compared to high-risk scores (EPclin Score > 3.3; OR 8.5×10-4 [95% CI 6.8×10-6, 6.0×10-3], p-value 5.7×10-68). All patients with high-risk scores received EET. Within the low-risk group, those treated with adjuvant chemotherapy and those who were lymph node positive chose to extend endocrine therapy at higher rates. The EPclin score provided significant information in predicting EET status, even when accounting for clinical variables such as node status, tumor grade, age at diagnosis, adjuvant chemotherapy status and tumor stage (EPclin Score OR 20.2 [10.1, 44.0]; p-value=3.1 × 10-25). Conclusions: Even after adjusting for other clinical factors, EndoPredict is a significant predictor of clinical decision on EET. High adherence to EndoPredict test results in EET decision making was noted in our study. Clinical trial information: NCT04016935. [Table: see text]