Project Summary Recent evidence suggests that up to 10% of patients with Pancreatic Ductal AdenoCarcinoma (PDAC) harbor a germline genetic mutation in a cancer risk gene. For this reason, the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) recommend germline genetic testing for all patients with PDAC. However, the best ways to perform this testing and use the resulting information remain unclear. As genetic testing becomes more common, critical questions need to be addressed: the number of genes to test; whether testing causes patient distress; and the benefit of PDAC screening in healthy mutation carriers. Answering these questions will maximize the benefit of genetic testing while minimizing the risks of over-testing, over-screening, and inefficient use of resources. My goal is to reduce the burden of pancreatic cancer by identifying optimal ways to execute germline genetic testing in patients with PDAC and act on the information gained. To accomplish this goal, I will develop a mathematical model that simulates patient genetic testing and resulting treatment selection, as well as family member notification, genetic testing, and PDAC screening (Aim 1). I will conduct patient surveys to expand our understanding of patient distress associated with genetic testing and communication of results to family members (Aim 2.1). I will use the model and insights gained to determine the timing and breadth of genetic testing that will optimize life expectancy for patients and family members (Aim 2.2). Finally, I will conduct a cost-effectiveness analysis of germline genetic testing in PDAC that takes into account diagnosis, treatment, and family genetic testing in an innovative structure (Aim 3). This will allow me to identify effective and high- value genetic testing strategies for patients with PDAC, including benefits to patients and their family members. Completion of this project will be a critical step towards my goal of becoming an independent clinician-scientist focused in disease modeling, genetic testing, and cancer outcomes research. In addition to my ongoing role as a clinician and teacher, I will undertake an educational program that has been specifically designed to support this project and my career goals. I have assembled a mentorship team with unique strengths in cancer modeling, cancer genetics, and pancreatic cancer research, all of whom are strong, independent investigators who can guide my career development. This award will provide critical support to allow me to broaden my knowledge base, leverage the expertise of a senior mentorship team, secure independent R01 funding, and support my transition to independence in the years to come.