50 Table 5: Interviews with Key Opinion Leaders Question Representative Responses Whatexcitingscientific opportunities do you see for advancing our understanding of metastasis? Basic biology • A deeper understanding of the biology of the steps of metastasis is needed to make improved, targeted treatments • For ER+ breast cancer, we need to understand more about late relapse and how best to treat it Translational and clinical research: • Significant preclinical literature points to our ability to prevent or slow metastasis, but not shrink overt metastatic tumors; to translate this we need drug- combination experiments and new clinical trials design • Developing more effective treatments for TNBC and IBC and controlling brain metastases are the biggest unmet medical need today related to MBC • For HER2+ breast cancer, we need to develop the safest long-term regimens for controlling the disease What do you think is the most promising target for developing new therapeutics aimed at metastasis? • The many targeted therapies in phase II and III MBC trials are among the most exciting (see Table 2). Still many more opportunities to identify new targets and combinations of targets are in the research stages • The therapeutics farthest along in drug development are CDK4/6 inhibitors, PARP inhibitors for BRCA carriers with breast cancer, and HSP90 inhibitors • All areas of new therapeutics outlined in your questions below are important; caution against picking only 1 or 2 as priority areas • We need to understand all of these as they relate to MBC o Cancer stem cells o Cell invasion o Cell signalling and proliferation as it relates to MBC o Tumor dormancy o Immune system o End organ microenvironment and the signals between the end organ and metastatic cell