Background: Breast cancer is the second leading cause of cancer death among women. The growth factor receptor HER2 is overexpressed in 20% to 30% of invasive breast cancers, and use of HER2-targeted therapies have improved responses and survival in patients with metastatic breast cancer (MBC). However, the choice of the most appropriate agents and their sequencing is crucial to maximizing beneficial patient outcomes. A study was conducted to determine if simulation-based educational interventions to address underlying clinical practice gaps could improve competence and performance of oncologists in the management of HER2-positive breast cancer. Methods: A cohort of US-practicing oncologists who participated in online simulation-based education was evaluated. The interventions consisted of two cases presented in a platform that allowed physician learners to assess the patient and choose from an extensive database of diagnostic possibilities matching the scope and depth of actual practice. Clinical decisions made by participants were analyzed using a sophisticated decision engine, and instantaneous clinical guidance was provided at each decision point employing current evidence-based and expert faculty recommendations. Participant decisions were collected after clinical guidance and compared with each user's baseline data using a 2-tailed paired T-test to provide P values for assessing the impact of simulation-based education on the clinical decisions made by participants as of 12/4/2014. Results: The assessment sample consisted of 123 oncologists who made clinical decisions within the simulation and proceeded to the concluding debrief section. As a result of clinical guidance provided through simulation, significant improvements were observed in several areas of management of patients with HER2-positive MBC, specifically: •35% improvement (P<.001) in the selection of the preferred treatment regimen (trastuzumab, pertuzumab, with a taxel) in the first-line setting •21% improvement (P=.003) in evidence-based treatment selection for individuals whose disease progressed on first-line therapy •A 35% decrease was seen in the number of participants who selected trastuzumab for individuals whose disease progressed on first-line therapy, which demonstrated an improvement in oncologists ability to select the most appropriate selection based on the current evidence-base •39% (P<.001) improvement in the number of oncologists who ordered adverse event counseling for the patient •Similarly, 33% more participants (P<.001) referred a patient for psychosocial counseling after clinical guidance The data gathered during simulation also provided insights into the remaining gaps, including the choice of the most appropriate, evidence-based first line HER2-targeted regimen in patients with MBC. Conclusion: This study showed improvements in evidence-based practice patterns of oncologists who were selecting therapeutic protocols for patients with HER2-positive MBC, thus demonstrating that simulation-based instruction can result in an increase in evidence-based clinical decisions and, therefore, may play a role in improving the quality of care and patient outcomes. Citation Format: Herrmann TL, Blevins D, Warters M, Peters P. Simulation in continuing professional development in oncologic care: Advancing evidence-based decisions in the management of HER2-positive metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-09-01.