Trastuzumab-based treatment is the standard care for patients with HER2+ metastatic breast cancer (MBC). About 10% of HER2+ MBC showed a long-term durable response (progression-free survival, PFS >3 years) to trastuzumab-based therapy. The aim of this study is to identify clinico-pathologic factors for a durable response to trastuzumab-based therapy in HER2-positive MBC. In the Yonsei Breast Cancer MBC Database, we identified 1218 MBC patients who were diagnosed from 2006 to 2015. Among them, 294 had HER2+ disease, and 153 received trastuzumab plus taxane chemotherapy as first-line treatment. Clinico-pathologic factors, such as hormone receptor (HR) status and metastatic sites, were reviewed. To evaluate a durable response, landmark analysis was performed. The median follow-up time was 28 months (95% CI 4.4-83.0 months). Of 153 HER2+ patients, there were 73 HR- patients (47.7%), and bone was the most common metastatic site. The median PFS and overall survival (OS) were 12 and 39 months, respectively. HR- patients showed a tendency toward longer PFS (median, 13 vs. 11 months, P = 0.160) compared with HR+ patients. Patients with non-visceral metastases had longer median PFS and OS than those with visceral disease (median PFS, 15 vs. 11 months, P = 0.012; median OS, 75 vs. 34 months, P = 0.03). Landmark analysis at 9 months suggested that the PFS of HR- patients was significantly longer than that of HR+ patients (median, 19 vs. 9 months, P = 0.008). Among patients with HER2+ MBC, HR status is a possible predictive biomarker of a durable response to trastuzumab-based therapy.