OBJECTIVES: As newer treatment options become available to postmenopausal women with HR+/HER2- metastatic breast cancer (mBC), understanding the relative survival benefit of different treatment options and sequencing is of increasing clinical importance. This study compared overall survival (OS) in patients with HR+/HER2- mBC whose 1^st-line therapy was endocrine therapy (1^st-line endo) vs. chemotherapy (1^st-line chemo) in real-world settings. METHODS: Data were extracted from a community oncology electronic medical records database from Altos Solutions. Eligible patients were postmenopausal women, with ≥1 medical record with a BC diagnosis, confirmed HR+/HER2- status, and 1^st mBC diagnosis (index date) after July 1, 2012. OS between 1^st-line endo and 1^st-line chemo patients was compared using cumulative proportion of deaths and Cox proportional hazard regressions controlling for age, race, region, insurance type, comorbidities, disease recurrence, and metastatic sites. RESULTS: Among the 1,051 patients meeting the eligibility criteria, 676 (64.3%) received 1^st-line endo and 375 (35.7%) received 1^st-line chemo. 1^st-line endo patients were older (68.1 vs. 64.4 years, p<0.001) and were more often Caucasian (74.1% vs. 65.9%, p=0.005) compared with 1^st-line chemo patients. Site of metastases was known in 57.5% of 1^st-line endo and 59.2% of 1^st-line chemo patients, with bone being the most common site (48.8% vs. 40.3%, p=0.008). The cumulative proportion of deaths was 5.9% vs. 10.7% (p=0.005), 10.4% vs. 14.7% (p=0.039), and 12.0% vs. 17.3% (p=0.016) at 6, 12, and 18 months, respectively. Patients receiving 1^st-line endo had better OS at 6 (adjusted hazard ratio [HR]: 0.50, p=0.004), 12 (HR: 0.60, p=0.009), and 18 (HR: 0.58, p=0.002) months compared to patients receiving 1^st-line chemo (patients with known site of metastases: 0.51 [p=0.031], 0.61 [p=0.049], and 0.63 [p=0.045], respectively) after adjusting for patient characteristics. CONCLUSIONS: Compared to chemotherapy, early endocrine therapy may be associated with better survival in postmenopausal women with HR+/HER2- mBC after adjusting for patient characteristics.