**3. Functional role of exosomes in breast cancer development**

Metastasis is the process by which primary tumor cells/tumor cells/cancer cells invade the surrounding tissues and colonize the blood vessels to proliferate and give rise to the tumor [28]. Controlling metastasis, which is mainly responsible for high patient mortality, is the main challenge in breast cancer therapy. Hence, several investigations are ongoing to understand the molecular mechanisms underlying metastasis in breast cancer. Recently, exosomes have attracted great attention as key players in regulating complex intracellular pathways from initiation to progression to metastasis in the development of breast cancer [29–31]. These mainly interact with the recipient cells in three ways: direct fusion with the cell membrane, interaction with the surface receptors, or internalization via endocytosis. Upon cellular uptake, exosomes deliver their cargo and initiate a cascade of events leading to various biological functions. Many breast cancer cell lines have been shown to release exosomes containing several proteins with signaling molecules, miRNAs, and long non-coding RNAs involved in migration, invasion, angiogenesis, and metastasis [32–34]. Proteomic profiling of exosomes secreted from breast cancer cell lines was shown to contain matrix metalloproteinases, which might be linked to the enhanced metastatic properties of breast cancer cells [32]. These findings suggest that exosomes act as key mediators in the tumor microenvironment by communicating various signaling molecules essential for breast cancer development [31].

Exosome-mediated transfer of genetic material from breast cancer cells has been shown to mediate resistance to chemotherapy and enhance tumor growth [35, 36]. Accumulating evidence suggests that exosomes may also play a role in the resistance of breast cancer radiotherapy and cancer immunotherapy [37, 38]. In breast cancer, drug-resistant cancer cells transmit resistance in drug-sensitive cells via the intercellular horizontal transfer of exosomal miRNAs [38]*.* Exosomes also transfer the drug efflux pump from docetaxel-resistant to sensitive ones in MCF-7 breast cancer cells [39]. Lv MM et al. showed that exosomes from drug-resistant cancer cells contain miRNAs that alter the phenotype of recipient breast cancer cells by altering their transcriptome [40]. Exosomes from stromal fibroblasts transmit non-coding RNA to breast cancer cells, thus contributing to treatment resistance by expanding therapy-resistant cells [41]. Thus, exosomes contribute to drug resistance in breast cancer.
