Background: The management of high-risk HER2-negative early-stage breast cancer (EBC) has recently evolved with the addition of newer agents including abemaciclib, olaparib, and pembrolizumab as (neo)adjuvant therapy options for appropriate patients. To aid healthcare professionals (HCPs) in the recommended implementation of these agents, we developed an online treatment decision support tool providing case-specific treatment guidance from 5 breast cancer experts. Here, we report an analysis of cases entered into the tool by HCPs, comparing their planned treatment with expert recommendations. Methods: Expert therapy recommendations for 10 case scenarios in high-risk HER2-negative EBC based on 3 pivotal clinical trials (KEYNOTE-522, OlympiA, and monarchE) were obtained in March 2022. Patient and disease characteristics included hormone receptor (HR) status, BRCA mutational status, lymph node positivity, presence of residual disease after resection, and additional criteria based on the 3 practice-changing trials. HCPs entered specific patient and disease factors into the tool along with their intended treatment plan and were shown 5 individual expert treatment recommendations for the unique case scenario. Results: From June 2022 to January 2023, 547 HCPs entered 982 patient case scenarios into the tool. A comparison of treatment recommendations by experts and HCPs showed divergence for several case scenarios. For patients with high-risk HR-positive/HER2-negative EBC and no BRCA mutation, all 5 experts recommended adjuvant abemaciclib plus endocrine therapy. By contrast, 64% of HCPs’ therapy choices were discordant with the experts, with 49% choosing chemotherapy followed by endocrine therapy. For patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy and have no residual disease, all 5 experts recommended observation, whereas 36% of HCPs recommended additional adjuvant therapy. In the setting of BRCA-mutated TNBC with residual disease after neoadjuvant pembrolizumab plus chemotherapy, 4 of 5 experts recommended adjuvant pembrolizumab plus olaparib, but just 33% of HCPs chose this combination. One third of HCPs who initially selected treatment options that diverged from expert recommendations or who were uncertain about treatment choice intend to change their therapy selection to align with the experts. Conclusions: Analysis of data from this tool suggests differences in clinical practice between experts and HCPs for multiple case scenarios of high-risk EBC, including examples of potential overtreatment. Moreover, our data demonstrate that this decision support tool may lead to better alignment of HCP treatment choices with experts, with the potential to improve clinical management of patients.