Breast cancer is the most common cancer and the leading cause of cancer death in women. Due to recent therapeutic progress allowing prolonged control of the disease, particularly at the metastatic stage, an increase in the incidence of cerebral metastases is currently observed for 5 to 30% of patients. Cerebral metastatic evolution is a poor prognostic factor since the median overall survival is estimated at around 7.4 months. Currently, mechanisms explaining cerebral tropism in breast cancers are not clearly identified, in particular, the overexpression of a membrane receptor involved in cell proliferation, HER2, or with a triple-negative phenotype (HER2^– and not expressing hormone receptors).

Exosomes are nanovesicles of 50–200 nm in diameter released into the extracellular environment via the endosomal pathway by fusion with the plasma membrane [1]. They are excreted in the physiological state by many types of cells as lymphocytes, epithelial cells, and dendritic cells, but also by tumor cells (tumors-derived exosomes / TDEs) [2, 3]. Their function is intercellular communication, in the same way as hormones, cytokines, and neurotransmitters. These extracellular nanovesicles are composed of a lipid bilayer with, in their lumen, numerous proteins, and genetic material. Exosomes are a direct cell reflection from which they derive and have the advantage of being found in biological fluids such as blood, urine, and saliva. In a tumor context, TDEs are very informative since they transport tumor genetic material of the mRNA and micro-RNA (miRNA) type, but also adhesion proteins, immunostimulation, and cytoskeleton molecules, enzymes, and Heat shock proteins (HSP) [4].

TDEs play a major role in the formation of primary tumors but also metastases [6]. Recent studies have shown the roles of exosomes in the development of premetastatic niches through the accumulation of extracellular matrix proteins from the primary tumor [7]. This specialized microenvironment can make the target organ conducive to metastatic cell colonization. Recently, it has been shown that cancer stem cells (CSCs) are capable of secreting exosomes, suggesting a significant role in tumor progression. Indeed, it has been demonstrated that TDEs have specific biological functions that can promote tumor growth and the occurrence of metastases, chemoresistance, and angiogenesis [8, 9]. Few studies have assessed CSC-derived exosomes’ role in tumor progression and brain metastasis formation in breast cancer [7, 10–12].

Our work will allow us to understand the interactions mediated by these exosomes and the tumor microenvironment to highlight new mechanisms involved in the loco-regional dissemination of primary brain tumors or the formation of brain metastases.