Breast Cancer Heterogeneity: A focus on Epigenetics and In Vitro 3D Model Systems.

Breast cancer (BC) is a widely prevalent form of neoplasia in women with fairly alarming mortality statistics. This aspect may be attributed, in part, to the current spatial and temporal heterogeneity-based limitations in therapies with possible recurrence of this tumour at primary and/or secondary sites. Such an extensive phenotypic heterogeneity in breast cancer is unlikely to be adequately or completely comprehended by an immuno-histopathology-based classification alone. This finding has warranted research and development in the area of microarray-based methods (i.e. transcriptomic and proteomic chips) for an improved molecular classification of this complex and heterogeneous tumour. Further, since epigenetics can also be an important determinant in terms of diagnosis, prognosis and therapy, this review provides an insight into the molecular portrait of BC in genetic and epigenetic terms. Specifically, the roles of characteristic DNA and histone-based modifications as well as mi-RNAbased alterations have been discussed with specific examples. Also, their involvement in epithelial mesenchymal transition (EMT) processes in cancer stem cells (CSCs) has been outlined. Last but not least, the salient aspects and the advantages of ex vivo/in vitro 3D model systems in recapitulating several aspects of BC tumour (particularly the architecture as well as the apico-basal polarity) are mentioned. This review hopes to provide not only an improved and updated understanding of the epigenetics of breast cancer, but to also elaborate on tumour model development/refinement, biomarker evaluation, drug resistance and test of individual drugs or drug combinations and drug delivery systems.