29 CHAPTER 2: Landscape Analysis of MBC Research Marc Hurlbert1 , Elly Cohen2 , Susan Colen2 , Stephanie Reffey3 , Kari Wojtanik3 , Musa Mayer4 , Samantha Finstad5 Katie McKenzie6 , Alison Butt7 , Ginny Mason8 , and Lynne Davies9 Avon Foundation for Women, 2 BreastCancerTrials.org, 3 Susan G. Komen, 4 AdvancedBC.org, 5 National Cancer Institute,6 California Breast Cancer Research Program, 7 National Breast Cancer Foundation (Australia), 8 Inflammatory Breast Cancer Research Foundation, and 9 International Cancer Research Partnership Abstract One part of the MBC Alliance’s mission is to advocate for and support research focusing on extending life, enhancing quality of life, and ultimately ending death from the disease. To inform these efforts we conducted a landscape analysis of MBC research by analyzing active clinical trials and previously funded research grants and conducting interviews with KOLs. Methods: We used a mixed-methods approach that included quantifying numbers of clinical trials and funded research grants and qualitative interviews with KOLs. We captured relevant aspects of the clinical trials and research grants for categorization and also assigned both trials and grants into the Hallmarks of Cancer framework[5] or Steps of Metastasis framework [6] , where feasible. Results: Clinical trials. We identified 224 clinical trials actively recruiting MBC patients through the NCI Physician Data Query (PDQ) dataset: 169 trials of targeted therapies, 35 chemotherapy trials, and 20 trials focusing on specific organ sites. Most (162) of the 169 trials of targeted therapies for MBC addressed 7 of the 10 hallmarks of cancer, including 95 trials of drugs that target sustained proliferative signaling and 27 trials of drugs that target immune escape mechanisms. Among the 169 targeted therapy trials there were 17 phase III trials, 54 phase II trials, and 96 phase I or phase I/II trials (note phase was not listed for 2 trials). We also identified 118 new drugs, vaccines, or combinations thereof being tested as targeted therapies, including 26 drugs targeting the PI3K/Akt/mTOR pathway, 20 targeting the epidermal growth factor receptor (ErbB) family, and 10 targeting hormone receptors. Grants. A search of 2 databases housing research grants from the majority of the cancer research funding organizations around the world revealed 20,800 funded research grants relevant to breast cancer, totaling $15.0 billion. Of these, we identified 2281 grants (11%), specifically relevant to MBC totalling $1.07 billion (7.1%). The majority of MBC grants focused on either invasion (36%, n=815) or metastatic colonization (29%, n=670); several other grants focused on multiple steps in metastasis (10%, n=238), whereas others could not be assigned to a specific step (13%, n=295). The grants relevant to MBC are predominantly basic research (69%), with some