Background: Endocrine therapy (ET) ± CDK 4/6 inhibitors is a common initial treatment for HR+/HER2-low (IHC 1+ or IHC2+/ISH-) metastatic breast cancer (mBC). However, many patients eventually progress on ET-based regimen and receive subsequent chemotherapy (CT). This study aimed to describe treatment patterns and outcomes following endocrine resistance among HR+/HER2-low mBC patients in U.S community oncology practices. Methods: Participating oncologists from Cardinal Health’s Oncology Provider Extended Network (OPEN) provided data from the medical charts of adult patients with HR+/HER2-low mBC who received at least two lines (2L) of systemic therapy, with first line (1L) initiated between Feb 19, 2016, and Dec 31, 2018. Analysis was performed among patients who received a subsequent chemotherapy (CT) after progression on their last observed line of ET-based regimen. Patient characteristics and treatment history were summarized descriptively. Kaplan-Meier analyses of treatment outcomes, including physician-reported real-world progression free survival (rwPFS), time to treatment response (TTR) and time to treatment discontinuation (TTD) were performed. Results: 150 HR+/HER2-low mBC patients who received subsequent chemotherapy after ET resistance were included [mean age: 61±11 years, 57.3% were white and 32.7% were black]. The proportion of patients who stopped ET after 1L, 2L and ≥3L of ET were 23.3% (n=35), 70.7% (n=106) and 6.0% (n=9), respectively. The mean duration of ET-based regimens was 29.7 (SD: 13.12) months. Among patients who stopped ET after 1L (n=35), most patients received fulvestrant + palbociclib (48.6%) in 1L prior to switching to CT. Among those who stopped ET after 2 or more lines (n=115), most patients received letrozole + palbociclib (57.4%) in 1L and fulvestrant (46.1%) in 2L. The most common CT regimen utilized was capecitabine (47.0%) followed by paclitaxel (28.0%). The median rwPFS on CT was 8.12 months (95% CI 7.36-9.24), with slightly shorter median rwPFS among those who stopped ET after 1L (7.82 months, 95% CI 7.07-9.53) vs. 2L+ (8.19 months, 95% CI 6.97-9.99). The median TTD of CT was 7.82 months (95% CI 7.07-8.61) and TTR was 4.96 months (95% CI 4.24-5.72), with similar estimates observed between patients who stopped ET after 1L and 2L+. Conclusions: In this small sample of HR+/HER2-low mBC patients, most patients switched to CT after receiving two lines of ET based regimens. Following ET resistance, durability of response with subsequent CT was short and similar irrespective of number of prior lines of ET based regimens. This preliminary chart review study highlights the unmet need for a more effective therapeutic alternative to CT after ET for HR+/HER2-low mBC patients. Further research using larger sample and more robust clinical data is warranted to confirm the study findings.