Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse

Breast cancer remains a leading cause of cancer-related death in women worldwide. Emerging evidence highlights the central roles of breast cancer stem cells (BCSCs) and circulating tumor cells (CTCs) in tumor initiation, progression, therapeutic resistance, and metastasis. BCSCs self-renew and drive intertumoral heterogeneity, while CTCs disseminate from primary tumors into the bloodstream, seeding distant sites. These populations share molecular features, including stemness and epithelial-mesenchymal transition markers, supporting the concept that a subset of CTCs acquires stem-like traits, enhancing metastatic potential and resistance to standard therapies. This review synthesizes current knowledge on BCSC molecular programs, key signaling pathways (e.g., Wnt, Notch, Hedgehog, Janus kinase/signal transducer and activator of transcription), and microenvironmental interactions that sustain stemness. It also examines mechanisms of CTC intravasation, state-dependent detection strategies, and their diagnostic and prognostic utility. We further highlight the adaptive plasticity of cancer stem cell-like CTCs, their contributions to drug resistance, and opportunities to target these phenotypes for personalized treatment. Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination. As multimodal detection improves and functional profiling matures, integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.