Abstract

Breast cancer risk is shaped not only by inherited genetic variation but also by dynamic and potentially reversible 
epigenomic modifications that reflect environmental exposures, ageing, and life-course influences. Epigenomic 
profiling, particularly DNA methylation analysis, has emerged as a promising tool for breast cancer risk 
stratification, early detection, and personalized screening strategies. This review examines the clinical validity and 
clinical utility of epigenomic biomarkers in breast cancer and explores their implications for population screening 
and health policy. We discuss current epigenomic technologies, the biological basis of methylation-based risk 
prediction, and evidence supporting their capacity to identify individuals at elevated lifetime or early-onset breast 
cancer risk. The potential of epigenomic profiling to complement or transform mammography-based screening 
through personalized, risk-adapted pathways is critically assessed. Broader population-level considerations, 
including ethical, legal, economic, and health-system implementation challenges, are examined through lessons 
drawn from existing national screening programs. While epigenomic screening offers advantages in accessibility, 
acceptability, and predictive performance, significant barriers remain, including standardization, cost-effectiveness 
evaluation, regulatory oversight, and equitable access. Advancing epigenomic profiling from bench to population
level deployment will require robust longitudinal validation, multidisciplinary collaboration, and policy 
frameworks that balance innovation with public trust and health equity.