"Small extracellular vesicles: messengers at the service of breast cancer agenda in the primary and distant microenvironments"

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Breast cancer (BC) remains a leading cause of cancer-related mortality in women, with complex mechanisms driving its initiation, progression, and resistance to therapy. In recent years, the tumor microenvironment (TME) has gained attention for its critical role in shaping tumor behavior, where small extracellular vesicles (small EVs) have emerged as key mediators of intercellular communication. These vesicles carry a diverse cargo of proteins, lipids, DNA, and various non-coding RNAs-such as miR-21, miR-155, and miR-1246-mirroring the molecular status of their originating cells. This review highlights the roles of small EVs in immune modulation, stromal remodelling, and metastatic niche formation, emphasizing their contribution to therapy resistance and immune evasion. We discuss recent updates on EV biogenesis, characterisation and isolation techniques, such as ultracentrifugation, immunoaffinity and microfluidic systems. We also critically evaluate their potential for clinical application and how well they conform to the MISEV2023 guidelines. Furthermore, we examine small EVs as diagnostic tools in liquid biopsies and compare them with conventional methods such as mammography and tissue biopsies. We also discuss organotropism mediated by small EV cargo (e.g., integrins α6β4, αvβ5) and the diagnostic potential of protein and lipid signatures (e.g., PD-L1, CD63, and exosomal li

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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