Abstract 299P
Background
MicroRNAs (miRNAs) are involved in the regulation of immune response and play an important role in immune escape. We aimed to evaluate the differential expression of plasma miR-10b, miR-126, miR-19α, miR-20α and miR-155, which regulate the interaction of cancer and immune cells during immunosurveillance in early (eBC) and metastatic breast cancer (mBC). We also aimed to identify associations between miRNAs expression levels and outcomes in mBC treated with first-line chemotherapy.
Methods
Blood samples were obtained from patients with eBC (n=140) and mBC (n=63) before adjuvant and first-line chemotherapy, respectively. Plasma miRNA expression levels were assessed by qRT-PCR and expression was classified as high or low according to the median values. ROC curves were constructed and the predicted performance of miRNAs was assessed. JADBio (www.jadbio.com), an Automated Machine Learning system was used to create predictive models.
Results
No differences in miRNA expression levels were revealed among early and mBC patients. Binary logistic regression analysis using miRNAs expression values as a continuous variable, resulted in a 4-miRNAs panel (miR-19a, miR-20a, miR-126 and miR-155) that could discriminate early from mBC; ROC curve analysis for this combined model resulted in an AUC of 0.802. JADBio further confirmed the performance of the 4-miRNA panel to predict disease status with an AUC of 0.759. Patients with low miR-10b expression had shorter PFS and OS compared to patients with high expression (8 mo vs. 13 mo; p=0.0017 and 28 mo vs. 39.7 mo; p=0.042, respectively). In multivariate analysis, recurrent disease and low miR-10b expression independently predicted for shorter PFS (HR: 2.657; p=0.001 and HR: 1.920; p=0.017, respectively), whereas performance status 2 independently predicted for shorter OS (HR: 2.031; p=0.03).
Conclusions
Deregulated expression of circulating miRNAs involved in tumor-immune interactions can discriminate disease status in BC. MiR-10b which is involved in the natural killer cell-based immune response, independently predicts for poor outcome in mBC. Our results further support the notion that circulating miRNAs represent potentially useful biomarkers in BC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Hellenic Society of Medical Oncology (HESMO); Anticancer Research Support Association (ARSA).
Disclosure
All authors have declared no conflicts of interest.