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.
背景:乳腺癌仍是全球女性中最常见的恶性肿瘤,其特点是显著的遗传、分子和临床异质性。传统的临床前模型极大地促进了我们对肿瘤生物学的理解,但在重现人类肿瘤微环境(TME)、免疫及转移行为的复杂性方面始终存在不足。近年来,乳腺癌芯片(BCOC)作为一种强大的微工程系统应运而生,它能够在受控的三维微环境中整合患者来源的细胞、基质与免疫成分,以及灌注、缺氧和酸性环境等生理刺激。 目的:全面综述乳腺癌芯片的发展与应用,涵盖其制造材料、关键亚型(导管原位癌、管腔A型、三阴性)的生物学建模、动态的肿瘤-基质-免疫相互作用,以及向骨、肝、脑、肺和淋巴结的器官趋向性转移。 方法:我们以“乳腺癌”、“微流控系统”和“乳腺癌芯片”为主要检索词,从学术可信数据库(PubMed、Web of Science、Google Scholar)中筛选相关文献。 结果:我们重点讨论并强调了微流控系统如何以前所未有的生理相关性复现疾病进展的关键特征,如上皮-间质转化、血管侵袭、免疫逃逸和治疗抵抗。特别关注了微流控平台中液体活检技术的整合,用于对循环肿瘤细胞、游离核酸和外泌体进行无创、实时分析。 结论:鉴于监管层面正推动减少药物开发中的动物使用,乳腺癌芯片平台正站在精准肿瘤学新时代的前沿。通过将生物学保真度与工程创新相结合,这些系统在变革癌症研究、疗法筛选和个性化医疗方面具有巨大潜力。
Microengineered Breast Cancer Models: Shaping the Future of Personalized Oncology