# Circulating MicroRNA in Breast Cancer

## TL;DR

This paper reviews how circulating microRNAs (miRNAs) can help diagnose and treat breast cancer, especially in aggressive subtypes like triple-negative breast cancer.

## Contribution

The paper provides a comprehensive review of subtype-specific roles of circulating miRNAs in breast cancer and their potential as biomarkers and therapeutic targets.

## Key findings

- miR-21 and miR-155 are frequently identified as oncogenic miRNAs in breast cancer.
- miR-205 is reported as a tumor-suppressive miRNA reduced in breast cancer and circulation.
- Certain miRNAs show subtype-specific effects, such as miR-17-92 and miR-31 differing between TNBC and ER-positive breast cancer.

## Abstract

Breast cancer is the most common cancer type in women. Variability in hormone receptor expression creates different subtypes that vary in behavior, treatment response, and patient outcome. MicroRNA (miRNA) is a small molecule that regulates how genes are turned on and off in cells. Because of their small size, miRNAs can easily be released from the cells that generate them. Circulating miRNAs can influence cancer growth, spread, and immune interactions, but can also be analyzed as biomarkers for cancer diagnostics, prognosis and therapy guidance. This review summarizes how specific miRNAs contribute to breast cancer development, how their effects differ between tumor subtypes, and the clinical approaches to the use of miRNAs for diagnosis, prognosis, and therapy guidance.

Background/Objectives: Despite recent advances in breast cancer diagnostics, therapies and personalized medicine through genetic profiling, effective treatment of aggressive subtypes, particularly triple-negative breast cancer (TNBC), remains a considerable clinical challenge. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that influence tumor progression and are detectable extracellularly in biofluids, where they are typically protected within extracellular vesicles (e.g., exosomes) or associated with RNA-binding proteins and lipoprotein complexes. This review integrates current evidence on oncogenic and tumor-suppressive extracellular miRNAs in breast cancer, with emphasis on subtype-specific functions and potential clinical relevance as liquid-biopsy biomarkers and therapeutic targets. Methods: A PubMed-based literature review (January 2000–February 2026) was conducted using search terms combining “breast cancer” with “miRNA/microRNA” and “circulating/plasma/serum/exosomal/extracellular vesicle.” Studies were prioritized if they provided validated targets/mechanisms and/or human clinical evidence for diagnostic, prognostic, or predictive utility; discrepant findings were evaluated in a subtype-aware framework. Findings were organized into functional categories (e.g., EMT/metastasis, cell-cycle/DNA damage, immune modulation, and hormone/growth factor signaling). Clinical and translational studies evaluating circulating miRNAs for diagnosis, prognosis, treatment response, and toxicity prediction were synthesized, together with key pre-analytical and analytical variables that affect reproducibility. Results: Across mechanistic and clinical studies, miR-21 and miR-155 recur as prominent oncogenic miRNAs, whereas miR-205 is frequently reported as a tumor-suppressive miRNA that is reduced in breast cancer and in circulation in several cohorts. Panels combining these miRNAs show promise for sensitive and specific breast cancer diagnostics. Additionally, several miRNAs show context- or subtype-dependent effects, with opposing activities reported between TNBC and estrogen receptor (ER)-positive disease (e.g., miR-17-92, miR-425, miR-181 family members, miR-31, and miR-24). Conclusions: Circulating miRNAs represent a promising class of minimally invasive biomarkers and potential therapeutic targets; however, translation is constrained by biological context dependence and by pre-analytical and analytical variability. Standardized protocols and rigorously validated, subtype-aware biomarker panels will be essential for clinical implementation and for enabling miRNA-informed precision oncology in breast cancer.