53 Are there other aspects of MBC research we should discuss? • In vitro models of MBC are insufficient; we need reproducible in vivo models of MBC • Need a better understanding of the natural history of MBC • Need to understand whether a metastatic cell is truly a cancer or aggressive cell; for example, in pancreatic cancer there are “metastatic” cells that are from non- cancerous hyperplasia (equivalent to DCIS or ADH in the breast)—that is, they have become metastatic but are not yet designated a cancer cell; whether this same phenomenon happens in breast hyperplasia is unknown • Reproducibility is key; several labs share cell lines and animal models of MBC that other labs have used incorrectly, thus drawing incorrect conclusions in their research publications • Important to look at the whole person, not just the primary tumor or metastatic site; for example, we now know that giving prophylactic antibiotics during chemotherapy may result in worse outcomes, because the patient’s microbiome is disturbed; need to study what role the microbiome has in health, immune function, response to therapy, etc. Abbreviations: ADH = atypical ductal hyperplasia, BC= breast cancer, CDK4/6 = cyclin-dependent kinase 4/6, CTC = circulating tumor cells, ctDNA = circulating tumor DNA, DCIS = ductal carcinoma in situ, ER+ = estrogen receptor positive breast cancer, HER2+ = human epidermal growth factor receptor2–positive breast cancer, HSP90 = heat shock protein 90, IBC = inflammatory breast cancer, MBC = metastatic breast cancer, PARP = poly-ADP ribose polymerase, PI3K = phosphatidylinositide 3-kinase, RECIST = Response Evaluation Criteria in Solid Tumors, TNBC = triple negative breast cancer.