Microengineered Breast Cancer Models: Shaping the Future of Personalized Oncology

Background: Breast cancer remains the most prevalent malignancy in women worldwide, characterized by remarkable genetic, molecular, and clinical heterogeneity. Traditional preclinical models have significantly advanced our understanding of tumor biology, yet consistently fall short in recapitulating the complexity of the human tumor microenvironment (TME), immune, and metastatic behavior. In recent years, breast cancer-on-a-chip (BCOC) have emerged as powerful microengineered systems that integrate patient-derived cells, stromal and immune components, and physiological stimuli such as perfusion, hypoxia, and acidic milieu within controlled three-dimensional microenvironments. Aim: To comprehensively review the BCOC development and application, encompassing fabrication materials, biological modeling of key subtypes (DCIS, luminal A, triple-negative), dynamic tumor-stroma-immune crosstalk, and organotropic metastasis to bone, liver, brain, lungs, and lymph nodes. Methods: We selected papers from academic trusted databases (PubMed, Web of Science, Google Scholar) by using Breast Cancer, Microfluidic System, and Breast Cancer on a Chip as the main search terms. Results: We critically discuss and highlight how microfluidic systems replicate essential features of disease progression-such as epithelial-to-mesenchymal transition, vascular invasion, immune evasion, and therapy resistance-with unprecedented physiological relevance. Special attention has been paid to the integration of liquid biopsy technologies within microfluidic platforms for non-invasive, real-time analysis of circulating tumor cells, cell-free nucleic acids, and exosomes. Conclusions: In light of regulatory momentum toward reducing animal use in drug development, BCOC platforms stand at the forefront of a new era in precision oncology. By bridging biological fidelity with engineering innovation, these systems hold immense potential to transform cancer research, therapy screening, and personalized medicine.