Circulating miR-200 family as predictive markers during systemic therapy of metastatic breast cancer

Abstract

Purpose Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS). Methods Forty-seven patients with metastatic breast cancer from the University Women’s Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated. Results Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS. Conclusion Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy.

Circulating miR-200 Family and CTCs in Metastatic Breast Cancer before, during, and after a New Line of Systemic Treatment

“…The present study enrolled 47 patients with MBC. Patient and tumor characteristics have been reported in a previous article and can be found in the supplementary material (Supplementary Material, Table S1 ) [ 30 ]. At study entry, on average, participants were 57 years old (Range: 35–89).…”

“…Blood plasma sampling, cell-free RNA isolation as well as cell-free miRNA detection were performed as described previously [ 30 ]. The expression levels of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 were measured, respectively, at the three following consecutive time points in the plasma of 47 patients with MBC: (1) at baseline before the start of a new line of systemic therapy (BL, miRNA BL ), (2) after the first completed cycle of a new line of systemic therapy (1C, miRNA 1C ), and (3) at the radiologically confirmed progression of the disease (PD, miRNA PD ).…”

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

“… MiR-200: this is a miRNA that is involved in the invasion and metastasis of breast cancer through the regulation of EMT (epithelial-mesenchymal transition) processes. Increasing miR-200 expression has been shown to reduce the ability of cancer cells to invade and migrate, making it a potential therapeutic target [ 183 , 184 ]. MiR-10b: it has been shown that miR-10b is involved in the metastasis of breast cancer through the regulation of EMT processes.…”

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

“…High levels of circulating miR-200c and miR-141 were associated with the poor OS of colon cancer patients [ 30 ]. Circulating miR-200 family members could predict OS and PFS in patients undergoing systemic therapy for metastatic breast cancer [ 31 ]. High levels of miR200 family members were strongly associated with reduced OS and PFS [ 31 ].…”

“…Circulating miR-200 family members could predict OS and PFS in patients undergoing systemic therapy for metastatic breast cancer [ 31 ]. High levels of miR200 family members were strongly associated with reduced OS and PFS [ 31 ]. These reports indicate that the miR-200 family could serve as both diagnostic and prognostic markers.…”