e12533 Background: Despite improved management of HR+/HER2− EBC, pts experience recurrences while on or up to decades after ending standard-of-care (SOC) ET. Addition of adjuvant (adj) cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), ribociclib and abemaciclib, to SOC ET resulted in significant improvement of outcomes in pts with HR+/HER2− EBC at risk of recurrence. In NATALEE, ribociclib showed invasive disease-free survival (iDFS) benefit in a broader population, including select node-negative (N0) disease. This RW study describes short-term recurrence in pts with HR+/HER2− stage II-III EBC treated with SOC adj ET ± chemotherapy (CT) in the last decade in the US, prior to use of adj CDK4/6is. Methods: A medical record review from large academic (Memorial Sloan Kettering Cancer Center) and community (Tennessee Oncology) oncology practices was conducted. Adult women with stage II-III HR+/HER2− BC (AJCC 8) who underwent surgical resection and initiated adj ET between Jan 2012 and Dec 2018 were included. Pts were randomly selected for equal distribution by year of adj ET initiation. Study measures were summarized descriptively. Kaplan-Meier method was used to estimate 3-, 5-, and 7-y iDFS and distant disease–free survival (DDFS). Results: Medical charts of 992 pts were analyzed (median follow-up from initiation of adj ET, 6.3 y). Median age was 58 y. Most pts (76.7%) had stage II disease at diagnosis, 64.0% received CT, and 34.2% were premenopausal. In total, 35.8% of pts were N0. Among all N0 pts, ≈41.4% had high-risk tumor features, as defined by NATALEE: >5 cm, 9.3%; 2-5 cm with G3, 25.9%; 2-5 cm with G2 + high genomic risk, estimated at 6.2%. N1(1-3) and N2/N3 (≥4) involvement was seen in 46.8% and 17.4% of pts, respectively. Analyses of iDFS/DDFS showed cumulative risk of invasive disease recurrence, predominantly distant disease, over 7 y in 21.4% across all stage II/III pts and 25.7% among the N0 pts meeting NATALEE criteria. Conclusions: This RW analysis from 2 major academic and community centers in the US confirms pts with stage II-III HR+/HER2− EBC, including select pts with N0 disease, experience considerable risk of recurrence, as early as during the adj treatment period cumulating over time. These findings warrant the consideration for tolerable treatment escalation for pts with stage II-III HR+/HER2− EBC.