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Updated: Jun 16, 2026
Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
Liquid biopsy utilizing miRNA in patients with advanced breast cancer treated with cyclin‑dependent kinase 4/6
Marcin Kubeczko1, Patrycja Tudrej2, Tomasz Tyszkiewicz2
1Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Upper Silesia 44-102, Poland.
Abstract:
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are the mainstay of treatment of hormone receptor+/human epidermal growth factor receptor 2-patients with advanced breast cancer (ABC). Despite improvements in overall survival, most patients experience disease progression. Biomarkers derived from a liquid biopsy are appealing for their potential to detect resistance to treatment earlier than computed tomography imaging. However, clinical data concerning microRNAs (miRNAs/miRs) in the context of CDK4/6is are lacking. Thus, the present study assessed the use of miRNAs in patients with ABC treated with CDK4/6is. Patients treated for ABC with CDK4/6is between June and August 2022 were eligible. miRNA expression analyses were performed using a TaqMan™ low-density miRNA array. A total of 80 consecutive patients with ABC treated with CDK4/6is at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) were assessed, with 14 patients diagnosed with progressive disease at the time of sampling, 55 patients exhibited clinical benefit from CDK4/6i treatment and 11 patients were at the beginning of CDK4/6i treatment. Patients with disease progression had significantly higher levels of miR-21 (P=0.027), miR-34a (P=0.011), miR-193b (P=0.032), miR-200a (P=0.027) and miR-200b (P=0.003) compared with patients who benefitted from CDK4/6i treatment. Significantly higher levels of miR-34a expression were observed in patients with progressive disease than in patients beginning treatment (P=0.031). The present study demonstrated the potential innovative role of circulating miRNAs during CDK4/6i treatment. Plasma-based expression of miR-21, -34a, -193b, -200a and -200b effectively distinguished patients with ABC who responded to CDK4/6i treatment from patients who were resistant. However, longitudinal studies are required to verify the predictive and prognostic potential of miRNA.
Insights
Circulating microRNAs (miRNAs) show promise as early biomarkers for detecting resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in advanced breast cancer (ABC). Specific miRNAs, including miR-21 and miR-34a, were elevated in patients with progressive disease, indicating potential for monitoring treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are standard treatment for hormone receptor-positive, HER2-negative advanced breast cancer (ABC).
- Despite treatment benefits, disease progression remains a challenge, necessitating early detection of resistance.
- Liquid biopsy-derived biomarkers, particularly microRNAs (miRNAs), offer potential for early resistance detection, but clinical data are limited.
Purpose of the Study:
- To investigate the role of circulating miRNAs as potential biomarkers for treatment response in patients with ABC receiving CDK4/6 inhibitors.
- To identify specific miRNAs whose plasma levels can differentiate between responders and non-responders to CDK4/6 inhibitor therapy.
Main Methods:
- Analysis of miRNA expression in 80 patients with ABC treated with CDK4/6is.
- Utilized TaqMan™ low-density miRNA arrays for miRNA profiling.
- Compared miRNA levels between patients with progressive disease, clinical benefit, and those initiating treatment.
Main Results:
- Patients with progressive disease showed significantly higher levels of miR-21, miR-34a, miR-193b, miR-200a, and miR-200b compared to those benefiting from treatment.
- Elevated miR-34a expression was also observed in patients with progressive disease versus those starting treatment.
- Plasma levels of miR-21, -34a, -193b, -200a, and -200b could distinguish between patients responding to CDK4/6is and those resistant.
Conclusions:
- Circulating miRNAs, specifically miR-21, -34a, -193b, -200a, and -200b, demonstrate potential as innovative biomarkers for monitoring CDK4/6 inhibitor treatment in advanced breast cancer.
- These miRNAs can differentiate treatment responders from non-responders.
- Longitudinal studies are needed to confirm the predictive and prognostic value of these miRNA biomarkers.
