Advancing Breast Cancer Heterogeneity Analysis: Insights from Genomics, Transcriptomics and Proteomics at Bulk and Single-Cell Levels

SIMPLE SUMMARY: This review discusses the heterogeneity of breast cancer and strategies to understand it using multi-omics profiling methods at the traditional bulk and single-cell levels. It begins with the exploration of genomics and its role in classifying breast cancer into molecular subtypes. Following that, it delves into the contribution of transcriptomics in illuminating the diverse gene expression patterns within individual breast cancer cells, further underscoring the disease’s complexity. The narrative then addresses the impact of proteomics, which unveils intricate protein expression patterns and modifications. Despite these advancements, it is essential to integrate multiple omics approaches to fully unravel breast cancer heterogeneity. The integration of genomics, transcriptomics, and proteomics at the single-cell level holds great promise for advancing breast cancer research and management in the future. ABSTRACT: Breast cancer continues to pose a significant healthcare challenge worldwide for its inherent molecular heterogeneity. This review offers an in-depth assessment of the molecular profiling undertaken to understand this heterogeneity, focusing on multi-omics strategies applied both in traditional bulk and single-cell levels. Genomic investigations have profoundly informed our comprehension of breast cancer, enabling its categorization into six intrinsic molecular subtypes. Beyond genomics, transcriptomics has rendered deeper insights into the gene expression landscape of breast cancer cells. It has also facilitated the formulation of more precise predictive and prognostic models, thereby enriching the field of personalized medicine in breast cancer. The comparison between traditional and single-cell transcriptomics has identified unique gene expression patterns and facilitated the understanding of cell-to-cell variability. Proteomics provides further insights into breast cancer subtypes by illuminating intricate protein expression patterns and their post-translational modifications. The adoption of single-cell proteomics has been instrumental in this regard, revealing the complex dynamics of protein regulation and interaction. Despite these advancements, this review underscores the need for a holistic integration of multiple ‘omics’ strategies to fully decipher breast cancer heterogeneity. Such integration not only ensures a comprehensive understanding of breast cancer’s molecular complexities, but also promotes the development of personalized treatment strategies.