Despite advances in treatments for breast cancer, metastatic breast cancer remains an incurable disease that results in 40,000 deaths per year in the US. Although some patients already have metastatic disease when they are first diagnosed, other cases of breast cancer recur and metastasize months or even years after an initial course of treatment that appeared to eradicate the primary tumor. Understanding where and how these tumor cells hide out and remain dormant for long periods of time, as well as how they are reactivated and why they are so resistant to therapy, is critical for developing new treatment strategies for this lethal disease. One of the critical challenges that has hindered the study of dormant tumor cells is the difficulty of accessing samples of these cells to study. To address these questions, the Welm lab has inaugurated a rapid autopsy program of patients with metastatic breast cancer to enable the direct study of these cells in their natural environment. Rapid autopsy is a coordinated effort in which pathologists and scientists work together to extract and analyze tissues from a patient shortly after death. Through the application of state-of-the-art genomics techniques and ex vivo patient-derived tumor modeling, the Welm lab will conduct the first characterization of active human breast cancer metastases in parallel with analysis of dormant tumor cells in the same individuals. This project will begin to answer questions about why some cancer cells stay dormant and why some grow into active metastases. It will also generate new hypotheses about how to prevent the outgrowth of dormant tumor cells that leads to cancer recurrence and death.