52 What role do you see for markers or circulating tumor cells (CTCs)? • Clinical utility of CTCs and ctDNA remains unproven, but they are useful tools for the research setting and can be prognostic in some clinical settings, however we still do not understand whether they are biologically useful • What do CTCs/ctDNA represent? Are they from primary tumors? From metastatic tumors? Both? • The source of these cells or ctDNA now in circulation is unknown Can you describe the challenges in designing and conducting clinical trials for MBC? Endpoints • New clinical trial designs are needed that address endpoints beyond tumor shrinkage and the RECIST scale; consider time to secondary metastasis or time to first metastasis in early breast cancer • Consider how many patients had lesion growth or shrinkage, how many had a secondary metastatic site develop; and consider progression-free survival studies in early metastatic disease • Quality of life measures need to be a part of all clinical trials Drugs/experimental therapeutics • Preclinical studies show that several agents can prevent or slow metastasis; need to translate these findings into clinical trial design • Current drugs in solid tumors do not work very well; there is too much industry influence driving clinical trials, which has trickled down into academia; progression-free survival and other endpoints are meaningless if the drugs do not significantly extend life span and quality of life • There is duplication in clinical research; for example, too many “me-too” drugs are being developed in industry (e.g., PI3K inhibitors) Recruitment for MBC trials in the US is challenging; patients need easier access to trial information—should review the steps the United Kingdom took to triple the number of cancer patients on trials from 4% to 12% • In general, screening is not aimed at early detection of metastasis, largely because in the past there were few treatment options; it is worth reconsidering this approach • There are too many solo investigators who design, execute, complete and publish single-center phase II trials; most likely this is required for promotion of clinical investigators; the reward system in academia needs to change to reward multicenter, multi-investigator, collaborative phase II trials