Patients With Luminal Breast Carcinoma: The State of the Field in Proteomic and Proteogenomic Molecular Subtyping

The subtyping of breast carcinoma (BC) is essential for an accurate diagnosis, prognosis, and treatment decisions. Histopathological evaluation and immunohistochemical analysis are standard methods for clinical stratification of patients with BC. Gene expression profiling (such as PAM50) can further provide a more comprehensive tumor description by examining disease-related processes at the transcript level. As such molecular events may not necessarily culminate in the synthesis of a mature proteins, proteomic analysis can help to reveal key molecular signatures, post-translational modifications, signaling pathways, and protein-protein interaction networks for even better characterization of the tumor and its microenvironment. Ultimately, by combining next-generation DNA and RNA sequencing with proteomic profiling toward an integrative proteogenomic framework, expressed mutant genes, copy number alterations, reconstructed RNA transcripts, alternative splicing events, and novel candidate biomarker proteins can be systematically analyzed. In this work, proteomic and proteogenomic studies (2015-2025) of luminal breast carcinoma (Lum BC) subtypes performed on tissues and body fluids were systematically reviewed with the aim of discussing protein signatures and molecular pathways they regulate, while the provided tables describe and compare the experimental platforms used. Future research must balance experimental complexity, proteomic and proteogenomic depth, and the time and cost of large-scale longitudinal studies while still producing datasets of sufficient quality. Here, emerging analyses of tumor-derived blood samples can provide "non-invasive" candidate biomarker proteins that may compete with tissue-derived protein signatures.