Molecular Characterization and Landscape of Breast cancer Models from a multi-omics Perspective

Breast cancer is well-known to be a highly heterogenous disease. This facet of cancer makes finding a research model that mirrors the disparate intrinsic features challenging. With advances in multi-omics technologies, establishing parallels between the various models and human tumors is increasingly intricate. Here we review the various model systems and their relation to primary breast tumors using available omics data platforms. Among the research models reviewed here, breast cancer cell lines have the least resemblance to human tumors since they have accumulated many mutations and copy number alterations during their long use. Moreover, individual proteomic and metabolomic profiles do not overlap with the molecular landscape of breast cancer. Interestingly, omics analysis revealed that the initial subtype classification of some breast cancer cell lines was inappropriate. In cell lines the major subtypes are all well represented and share some features with primary tumors. In contrast, patient-derived xenografts (PDX) and patient-derived organoids (PDO) are superior in mirroring human breast cancers at many levels, making them suitable models for drug screening and molecular analysis. While patient derived organoids are spread across luminal, basal- and normal-like subtypes, the PDX samples were initially largely basal but other subtypes have been increasingly described. Murine models offer heterogenous tumor landscapes, inter and intra-model heterogeneity, and give rise to tumors of different phenotypes and histology. Murine models have a reduced mutational burden compared to human breast cancer but share some transcriptomic resemblance, and representation of many breast cancer subtypes can be found among the variety subtypes. To date, while mammospheres and three- dimensional cultures lack comprehensive omics data, these are excellent models for the study of stem cells, cell fate decision and differentiation, and have also been used for drug screening. Therefore, this review explores the molecular landscapes and characterization of breast cancer research models by comparing recent published multi-omics data and analysis.