ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 11 University of Wisconsin-Madison’s Exceptional Survivor Study. Recently, the University of Wisconsin-Madison launched the only known study dedicated solely to exceptional survivors to determine why MBC patients have lived an unusually long time since their original early stage breast cancer or de novo MBC diagnosis. The underlying hypothesis relating to this definition is that early stage patients have had metastatic disease all along, but their tumor cells have remained dormant or extremely slow growing, and their metastatic disease has been clinically undetectable. This study will also include “de novo” MBC patients who were metastatic from the beginning. This hypothesis represents a different definition in terms of timing of diagnosis for exceptional survivors. As described in this paper, the MBCA defines exceptional survival as the time from the patient’s advanced stage cancer diagnosis to the current date. Dr. Mark Burkard, who is leading the University of Wisconsin-Madison study, wants to learn about the contributing factors that have enabled patients to live an unusually long time with breast cancer cells in their bodies. Specifically, Dr. Burkard has employed the following criteria for patient inclusion in his study: For MBC patients with ER+ disease: • Duration since early stage or de novo breast cancer diagnosis (overall survival) 10+ years For MBC patients with ER− disease (the study will distinguish between patients with HER2+ vs. TNBC after enrollment): • Duration since early stage or de novo breast cancer diagnosis (overall survival) 5+ years. This study is unique in that it is dedicated to understanding the factors leading to exceptional survival in metastatic patients, and that unlike many other studies, it does not limit the potential causative factors to genetics (although both germline and tumor mutations will be studied). Non- genetic factors will be explored via patient questionnaires, which will solicit information regarding factors such as lifestyle and co-morbidities. Furthermore, Dr. Burkard hopes to share de-identified patient data in as much detail as possible while maintaining patient privacy and anonymity. Memorial Sloan Kettering Cancer Center (MSKCC). Memorial Sloan Kettering Cancer Center is shifting the focus from failed clinical trials in which few patients responded well, and is reexamining the subset of patients in those trials who displayed a positive response (i.e., exceptional responders). MSKCC has established the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, which will be involved in sequencing samples from exceptional responders (read more). MSKCC is using next-generation sequencing of tumor tissue that allows detection of molecular aberrations in heterogeneous tissue to determine what makes these exceptionally responding tumors unique, and has established a tumor tissue bank that contains samples from thousands of cancer patients. MSKCC hypothesizes that if a particular aberration can be