OBJECTIVES/GOALS: Obesity is associated with increased incidence of breast cancer (BC), yet is not included in many lifetime-risk calculators. Obesity may impact breast cancer screening sensitivity. Retrospective studies show that bariatric surgery is associated with a lower risk of BC, but the effects of surgical weight loss on breast tissue are poorly understood. METHODS/STUDY POPULATION: We proposed a mixed-methods before and after study design to investigate the effects of surgical weight loss on breast tissue via pre- and post-weight loss breast tissue biopsies and imaging. In addition, we aimed to better understand barriers to BC screening for patients with obesity by conducting qualitative interviews. With institutional review board approval, we have begun recruiting 14 cisgender women who plan to undergo Roux-en-Y gastric bypass or sleeve gastrectomy. Participants must be at least 40 years old, with no prior history of breast biopsies or breast cancer and will undergo comprehensive breast cancer screening including mammography with quantitative density assessment, breast MRI, as well as breast core biopsies. RESULTS/ANTICIPATED RESULTS: We hypothesize that obesity and its associated metabolic changes lead to altered breast stroma, including increased inflammation, and tissue stiffness, with subsequent risk of carcinogenesis. If true, we expect to find obese women will have measurably increased inflammatory markers in their breast tissue, which are reduced after bariatric surgery. We expect that change in mammographic density may correlate with fibroglandular volume change on MRI; there are little data on change in background parenchymal enhancement in the setting of obesity and weight change and quantifying this will provide preliminary data for future work. Last, we expect that undergoing BC screening will be easier for patients after weight loss due to constraints of imaging equipment and potential bias in the screening process. DISCUSSION/SIGNIFICANCE: Screening for BC is paramount to improving outcomes yet people with obesity are screened less with worse outcomes. Studying the effects of weight loss on the breast may improve interpretation of breast imaging in the setting of obesity and identify markers of risk. Understanding barriers to screening may help us develop strategies to improve screening.