PURPOSE: To evaluate the role of Postoperative Radiotherapy (PORT) in HER2-positive metastatic breast cancer (MBC) in the context of targeted therapy and clarify the subgroups that may benefit from PORT. METHODS: Clinical data of female patients with HER2-positive MBC from the surveillance, epidemiology, and end results (SEER) database for the years 2016-2020 were collected according to established inclusion and exclusion criteria. The impact of PORT on patient survival was assessed, and subgroup analyses were performed to identify populations with potential benefits from PORT. RESULTS: A total of 541 patients from the SEER database were included in the analysis. The 3-year overall survival (OS) of the PORT group was significantly higher than that of the non-PORT group. (86.7% vs. 80.2%, P = 0.011). Multivariate analysis revealed that race and PORT were independent prognostic factors. Black patients and those who received PORT had longer overall survival (OS) (P <
0.05). Subgroup analysis suggested that PORT further improved OS in patients with mastectomy, advanced TN stage, high tumor grade, positive hormone receptor status, and multiple metastatic organs (P <
0.05). CONCLUSION: PORT further improves the survival of HER2-positive MBC. Subgroup analysis suggests that patients with locally advanced stage (T3-4, N2-3), Grade III, HR-positive status, bone-and-visceral metastasis, and those who have undergone mastectomy benefit significantly.