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Simple Summary  This review has comprehensively summarized the most recent studies in the last few years about exosomal microRNAs on metastasis of breast cancer (BC), systematically outlined and elucidated the pleiotropic roles that exosomal microRNAs take, and discussed the specific underlying mechanisms related. Besides, we also clearly demonstrate the clinical implications of exosomal microRNAs in various aspects, including early-stage discovery of BC, systematic and targeted therapy, and the selection of anti-cancer chemo-agents. This review clarifies the scope and extent of current studies about the relationship between exosomal microRNAs and metastasis of BC, laying a solid foundation for further laboratory studies. What’s more, it links the theoretical researches and clinical features about exosomal microRNAs on metastasis of BC together, providing novel clues for BC diagnosis, chemotherapeutics and drug efficacy evaluation in clinical, which indicates the great potential of exosomal microRNAs in clinical significance.    Abstract  As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed “exosomal microRNAs (miRNAs)”. Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.

Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives