This prospective, multicenter, non-interventional observational study is designed to investigate tissue- and serum-derived exosomal microRNA profiles and their association with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC).
Although established clinicopathological parameters, including hormone receptor status, Human Epidermal Growth Factor Receptor 2 (HER2) expression, and Ki-67 index, are routinely used to stratify breast cancer subtypes and provide important prognostic and predictive information, inter-patient variability in treatment response remains substantial. These parameters do not fully capture the dynamic biological heterogeneity of tumors or reliably predict individual response to neoadjuvant chemotherapy in all patients. This underscores the need for additional, minimally invasive molecular biomarkers that may complement existing clinicopathological factors and better reflect tumor biology, thereby supporting personalized therapeutic strategies.
Exosomes are small extracellular vesicles released by tumor and stromal cells that carry molecular cargo, including microRNAs, which reflect the biological activity of their cells of origin. Due to their stability and detectability in both tumor tissue and peripheral blood, exosomal microRNAs represent promising candidates for monitoring treatment response and identifying mechanisms of chemotherapy sensitivity or resistance.
In this study, patients with histologically confirmed locally advanced breast cancer who are scheduled to receive standard-of-care neoadjuvant chemotherapy will be prospectively enrolled. The study is strictly observational, and no additional interventions, blood draws, tissue biopsies, or sample collection procedures will be performed for research purposes. Exosomal miRNA analyses will be conducted exclusively on residual serum samples obtained during routine clinical blood tests and leftover tumor tissue collected for diagnostic or surgical purposes as part of standard clinical care.
Exosomal microRNA expression profiles derived from tissue and serum samples will be analyzed using molecular techniques and correlated with pathological complete response (pCR) following completion of neoadjuvant chemotherapy. Pathological response will be evaluated using established tumor regression grading systems, including pathological complete response (pCR) and standardized tumor regression grading criteria.
In addition, residual samples obtained from patients with histologically confirmed benign breast lesions will be included as a reference control group to assess the specificity of molecular alterations observed in malignant disease.
The primary objective of the study is to evaluate whether tissue- and serum-derived exosomal microRNA expression patterns are associated with pathological complete response (pCR) to neoadjuvant chemotherapy. Secondary objectives include comparing tissue- and serum-based exosomal microRNA profiles, exploring associations with clinicopathological variables, and assessing the potential of exosomal microRNAs as predictive biomarkers of treatment sensitivity or resistance.
