Emerging Genetic Biomarkers for Breast Cancer Diagnosis

Breast cancer remains a heterogeneous malignancy in which early detection and molecular stratification are critical for improving patient outcomes. While BRCA1 and BRCA2 mutations have historically defined hereditary risk, their predictive limitations have prompted the search for broader genomic and epigenomic markers. Recent advances in next-generation sequencing, liquid biopsy technologies, and multi-gene expression profiling have expanded the biomarker landscape, enabling more precise risk assessment and therapeutic decision-making. This review synthesizes current evidence on emerging genetic biomarkers with potential clinical utility. High-penetrance genes such as PALB2, CHEK2, ATM, and PIK3CA are increasingly recognized for their role in hereditary susceptibility, while moderate-risk variants in RAD51C/D and BARD1 refine individualized risk stratification. Liquid biopsy approaches, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), provide non-invasive, real-time monitoring of tumor dynamics and treatment response. Gene expression signatures (e.g., Oncotype DX, MammaPrint) have demonstrated prognostic value in predicting recurrence risk and guiding adjuvant therapy. Furthermore, epigenetic markers—such as DNA methylation profiles, microRNAs, and histone modifications—are emerging as promising diagnostic and predictive tools, reflecting tumor heterogeneity and microenvironmental influences. Collectively, these advances highlight a paradigm shift toward precision oncology, where integrated genomic and epigenomic data inform personalized screening, risk stratification, and therapeutic strategies. The incorporation of novel biomarkers into clinical practice has the potential to enhance early detection, optimize treatment selection, and improve long-term survival. Continued validation in large-scale, multi-ethnic cohorts and harmonization of biomarker-driven guidelines remain essential for translating these discoveries into routine cancer care