Abstract Background: The management of HER2-positive (HER2+) metastatic breast cancer (MBC) has continued to evolve, with multiple FDA approvals of novel HER2-targeted agents since late 2019. Considering the growing HER2+ MBC treatment armamentarium, we sought to identify current practice patterns among community healthcare professionals (HCPs) for HER2+ MBC by comparing HCP and key opinion leader (KOL) treatment recommendations using an online decision support tool. Methods: An online decision support tool was developed with input from 5 KOLs to provide therapy recommendations for 630 HER2+ MBC patient case scenarios based on conventional considerations including distribution of metastatic disease, treatment history, duration of response, and specific comorbidities. HCP tool users entered specific patient criteria to define a case along with their intended management for each case. The tool then showed 5 KOL recommendations for the user-entered patient case, and the users were asked to indicate if the expert recommendations confirmed or changed their intended approach. An analysis of expert recommendations and user-selected therapy was performed. Results: Between November 2022 and July 2023, 313 patient cases were entered by 242 participating HCPs. HCP and KOL treatment recommendations were frequently discordant (Table). For patients with de novo HER2+ MBC (n = 55), there was strong concordance (63%; P = .0001) between HCP and KOL recommendations. However, weak treatment selection concordance (53%; P < .0001) was observed for patients with disease progression after standard neoadjuvant/adjuvant therapy with chemotherapy plus HER2-targeted agents (n = 57). In the second-line setting, 43% concordance was observed for patients with non‒central nervous system (CNS) disease progression without CNS progression after first-line therapy with THP (n = 67; P < .0001), whereas 61% concordance was observed for patients with non-CNS and CNS disease progression after first-line therapy with THP (n = 61; P < .0001). In the third-line setting, 31% concordance was observed for patients with non-CNS disease progression without CNS progression (n = 32; P < .0001), and 47% concordance was observed for patients with non-CNS and CNS disease progression (n = 19; P = .0009). For HCPs whose treatment plan did not match KOL recommendations in these scenarios, 62% indicated that KOL recommendations confirmed or changed their intended therapy, but 19% indicated that there were barriers to implementing those recommendations. Conclusions: These data suggest ongoing challenges to optimally incorporate novel HER2-targeted therapies in the care of patients with HER2+ MBC, particularly in the second line and beyond, but an online tool providing KOL advice on specific patient scenarios confirmed or changed the clinical approach for a majority of HCPs. Thus, continued development of resources for HCPs, including online decision support tools, may be increasingly important given the rapidly evolving treatment landscape. Table. Summary of Treatment Choices by KOLs or HCPs for Select Patient Scenarios Citation Format: Kristen Rosenthal, Sara Hurvitz, Komal Jhaveri, Heather McArthur, Sara Tolaney, Timothy Quill. Contemporary HER2-Positive MBC Treatment Recommendations Among Community Healthcare Professionals: Analysis of an Online Interactive Decision Support Tool [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-08.