Breast cancer organoids and organoids-on-a-chip in drug development

Breast cancer is the most frequently diagnosed malignancy and a leading cause of cancer-related death in women. Although two-dimensional cell lines and patient-derived xenografts have long served as foundational models in breast cancer research, they fail to fully recapitulate tumor heterogeneity, the native tumor microenvironment, and clinically relevant drug responses. Patient-derived organoids and organoids-on-a-chip platforms overcome these limitations by preserving the genetic, histological, and functional characteristics of the parental tumor. This review summarizes how these models facilitate drug screening, elucidate the mechanisms underlying tumorigenesis and drug resistance, and are integrated with microfluidic technologies to advance personalized therapy. Particular emphasis is placed on traditional Chinese medicine. Patient-derived organoids provide a platform for investigating the multitarget activities of herbal compounds and formulae in patient-derived tissues, while syndrome-stratified models enable the study of pattern differentiation and Fuzheng-Quxie-mediated immune regulation at the cellular level. Finally, the remaining challenges in standardization, throughput, and microenvironmental fidelity are highlighted in the context of clinical translation.