Liquid Biopsy and Multi-Omic Biomarkers in Breast Cancer: Innovations in Early Detection, Therapy Guidance, and Disease Monitoring

Abstract

Liquid biopsy and multi-omic biomarker integration are transforming precision oncology in breast cancer, providing real-time, minimally invasive insights into tumor biology. By analyzing circulating tumor DNA, circulating tumor cells, exosomal non-coding RNAs, and proteomic or metabolomic profiles, clinicians can monitor clonal evolution, therapeutic response, and recurrence risk in real time. Recent advances in sequencing technologies, methylation profiling, and artificial intelligence-driven data integration have markedly improved diagnostic sensitivity and predictive accuracy. Multi-omic frameworks combining genomic, transcriptomic, and proteomic data enable early detection of resistance, molecular stratification, and identification of actionable targets, while machine learning models enhance outcome prediction and therapy optimization. Despite these advances, key challenges persist. Pre-analytical variability, lack of standardized protocols, and disparities in access continue to limit reproducibility and clinical adoption. High costs, incomplete regulatory validation, and the absence of definitive evidence for mortality reduction underscore the need for larger, prospective trials. Integrating multi-omic assays into clinical workflows will require robust bioinformatics pipelines, clinician-friendly reporting systems, and interdisciplinary collaboration among molecular scientists, data engineers, and oncologists. In the near future, liquid biopsy is expected to complement, not replace, traditional tissue analysis, serving as a cornerstone of adaptive cancer management. As sequencing becomes faster and more affordable, multi-omic and AI-driven analyses will allow earlier detection, more precise treatment adjustments, and continuous monitoring across the disease course. Ultimately, these innovations herald a shift toward real-time, data-driven oncology that personalizes breast cancer care and improves patient outcomes.

Keywords: breast cancer; healthcare; liquid biopsy; multi-omic biomarkers; precision medicine.

Figure 1

Integrated role of liquid biopsy across diagnosis, treatment, and follow-up in breast cancer. During diagnosis and early detection, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and exosomal microRNAs enable early molecular identification of mutations and methylation changes that may precede imaging findings. In the treatment phase, quantitative ctDNA monitoring reflects therapeutic response and minimal residual disease, while circulating tumor cells (CTCs) and exosomal long non-coding RNAs provide insights into receptor discordance, epithelial–mesenchymal transition, and immune modulation. For follow-up and relapse surveillance, the reappearance of ESR1 or TP53 mutations and persistent CTCs serve as early indicators of recurrence or micrometastatic disease. Multi-omic integration and AI-based analytical tools further enhance the predictive accuracy of these biomarkers, supporting personalized and adaptive management strategies in breast cancer [37,39,84].