Exosomal MicroRNA-21 Expression Changes During Neoadjuvant Chemotherapy in Breast Cancer Patients

Abstract

Background: Variability in breast cancer response to neoadjuvant chemotherapy highlights the need for minimally invasive biomarkers capable of reflecting treatment effectiveness during therapy. Circulating exosomal microRNA-21 may provide dynamic molecular information because of its stability and association with tumor progression and treatment response. Objective: To evaluate longitudinal changes in circulating exosomal miR-21 during neoadjuvant chemotherapy and examine their association with tumor response. Methods: This parallel-group randomized controlled trial enrolled 72 women with stage II–III breast cancer at a tertiary-care oncology center in Punjab, Pakistan. Participants were allocated equally to protocolized exosome-guided monitoring or routine clinical monitoring. Blood was collected at baseline and before chemotherapy cycles for exosomal miR-21 quantification using quantitative reverse-transcription polymerase chain reaction. Final outcomes were available for 67 participants. Analyses included t-tests, repeated-measures analysis of variance, risk ratios, and Pearson correlation. Results: Post-treatment miR-21 expression was lower in the intervention group than in the control group (1.42±0.39 versus 2.11±0.53; mean difference=−0.69; 95% CI: −0.92 to −0.46; p<0.001). Tumor shrinkage was greater by 15.50 percentage points (95% CI: 6.80–24.20; p<0.001). RECIST response was 84.8% versus 64.7% (p=0.058), and pathological complete response was 39.4% versus 23.5% (p=0.162). miR-21 reduction correlated with tumor shrinkage (r=0.62; 95% CI: 0.45–0.75; p<0.001). Conclusion: Serial exosomal miR-21 measurement reflected treatment-associated molecular changes and was associated with radiological tumor reduction, but larger standardized trials are required before clinical implementation