Purpose: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed. Methods: Women who underwent Oncotype DX® testing between 2011-2014 with minimum 5-year follow-up were included. ‘Low risk’ was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent vs non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. Results: We identified 6 cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, 5 of 6 patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p=0.002) andwere more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p=0.006). In contrast, persistent patients were 10.3 times more likely to have been offeredsymptom-alleviating medications compared with non-persistent patients (pConclusions: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.