Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance

Breast cancer metastasis remains a leading cause of mortality. Animal models have been instrumental in dissecting the complex metastatic cascade and have provided insights into tumor progression and mechanisms of dissemination to distant organs. However, significant gaps remain, particularly in the context of a highly heterogeneous disease like breast cancer. This review summarizes animal models utilized to study breast cancer metastasis, including mutagen-induced and genetically engineered mouse models, cell line-based syngeneic and xenograft models, patient-derived xenografts, as well as rat and zebrafish models. We summarize the strengths and limitations of each model in recapitulating key stages of metastasis, including the onset of metastasis, organ-specific tropism, and tumor-microenvironment interactions. Additionally, we highlight the importance of these models in preclinical drug testing and personalized therapy. By providing a comprehensive overview, this review aims to guide researchers in choosing the most suitable preclinical breast cancer animal model to effectively address metastasis-related questions.