Small extracellular vesicles as system-level regulators and predictive biomarkers in breast cancer progression and chemoresistance.

Abstract

Small extracellular vesicles (sEVs) play a pivotal regulatory role in intercellular communication within breast cancer, coordinating tumor growth, microenvironment remodeling, immune modulation, and therapeutic response. Beyond serving as passive carriers of biomolecules, mounting evidence indicates that sEVs actively orchestrate the dynamic evolution of the tumor ecosystem through cargo specificity and cell-of-origin-dependent mechanisms. We synthesize recent research advances (2021-2025) to elucidate how nucleic acids, proteins, and lipids carried by sEVs integrate into key processes in breast cancer, including oncogenic signaling, epithelial-mesenchymal transition (EMT), metastasis microenvironment formation, immune evasion, and therapeutic resistance. We further highlight how their specificity and cellular origin provide a unified framework for reconciling reported functional heterogeneity in sEVs across studies. Building on this, we discuss emerging evidence demonstrating sEVs' role in reshaping tumor-immune and therapeutic ecosystems, promoting immune evasion, and facilitating horizontal transmission of drug-resistant phenotypes. Finally, we evaluate the translational potential of sEVs as biomarkers and therapeutic targets, proposing a conceptual framework for integrating sEV profiling into precision oncology strategies. This review positions sEVs as central regulators of breast cancer ecosystem dynamics, highlighting their potential in reshaping biomarker development and therapeutic innovation within precision oncology.