Abstract
Breast cancer is an individually unique, multi-faceted and chameleonic disease, an eternal challenge for the new era of high-integrated precision diagnostic and personalized oncomedicine. Besides traditional single-omics fields (such as genomics, epigenomics, transcriptomics and metabolomics) and multi-omics contributions (proteogenomics, proteotranscriptomics or reproductomics), several new "-omics" approaches and exciting proteomics subfields are contributing to basic and advanced understanding of these "multiple diseases termed breast cancer": phenomics/cellomics, connectomics and interactomics, secretomics, matrisomics, exosomics, angiomics, chaperomics and epichaperomics, phosphoproteomics, ubiquitinomics, metalloproteomics, terminomics, degradomics and metadegradomics, adhesomics, stressomics, microbiomics, immunomics, salivaomics, materiomics and other biomics. Throughout the extremely complex neoplastic process, a Breast Cancer Cell Continuum Concept (BCCCC) has been modeled in this review as a spatio-temporal and holistic approach, as long as the breast cancer represents a complex cascade comprising successively integrated populations of heterogeneous tumor and cancer-associated cells, that reflect the carcinoma's progression from a "driving mutation" and formation of the breast primary tumor, toward the distant secondary tumors in different tissues and organs, via circulating tumor cell populations. This BCCCC is widely sustained by a Breast Cancer Proteomic Continuum Concept (BCPCC), where each phenotype of neoplastic and tumor-associated cells is characterized by a changing and adaptive proteomic profile detected in solid and liquid minimal invasive biopsies by complex proteomics approaches. Such a profile is created, beginning with the proteomic landscape of different neoplastic cell populations and cancer-associated cells, followed by subsequent analysis of protein biomarkers involved in epithelial-mesenchymal transition and intravasation, circulating tumor cell proteomics, and, finally, by protein biomarkers that highlight the extravasation and distant metastatic invasion. Proteomics technologies are producing important data in breast cancer diagnostic, prognostic, and predictive biomarkers discovery and validation, are detecting genetic aberrations at the proteome level, describing functional and regulatory pathways and emphasizing specific protein and peptide profiles in human tissues, biological fluids, cell lines and animal models. Also, proteomics can identify different breast cancer subtypes and specific protein and proteoform expression, can assess the efficacy of cancer therapies at cellular and tissular level and can even identify new therapeutic target proteins in clinical studies.