Aberrant Transcription-Factor Expression and Regulatory microRNAs in Metastatic Breast Cancer

Metastatic breast cancer is driven by reversible cell-state programs shaped by transcription factors (TFs) and microRNAs (miRNAs). Dysregulated TFs integrate oncogenic signaling, hypoxia, inflammation, lineage identity, mechanical cues, and chromatin state, whereas miRNAs buffer or reinforce these programs through post-transcriptional repression. Their reciprocal interactions form dynamic regulatory circuits controlling epithelial–mesenchymal plasticity, stem-like behavior, invasion, dissemination, dormancy, organ-specific colonization, immune escape, and treatment resistance. This narrative review examines major TF-miRNA modules implicated in breast cancer metastasis, including ZEB1/2-miR-200/miR-205, TWIST1-miR-10b, MYC-miR-9, FRA-1-miR-34, FOXM1-miR-671-5p, HIF-1α-miR-18a, mutant p53/HIF-1α-miR-30d, STAT3-miR-21/miR-34a, and the context-dependent FOXP3-miR-200c/miR-141 network. Evidence from experimental models, paired primary-metastatic tissues, circulating tumor cells, extracellular vesicles, and plasma cohorts is integrated with emphasis on disease stage, molecular subtype, and biological compartment. Tissue and circulating miRNA signals are not interchangeable, and FOXP3-miR-200c relationships appear compartment- and model-dependent. Clinical translation remains limited by tumor heterogeneity, pre-analytical variability, incomplete cellular resolution, and limited causal validation. Prospective, subtype-stratified studies integrating spatial, single-cell, metastatic-tissue, and standardized liquid-biopsy analyses are required before TF-miRNA signatures can guide clinical management.