Abstract

Population genomics is reshaping breast cancer prevention by enabling the identification of individuals and 
families at elevated genetic risk before disease onset. Advances in genomic technologies have made population
scale screening for high-penetrance breast cancer susceptibility genes, particularly BRCA1 and BRCA2, 
increasingly feasible. However, translating discoveries from bench to population requires careful attention to the 
return of results, cascade testing of at-risk relatives, and the readiness of health systems to deliver these 
interventions equitably and effectively. This review examines population genomics for breast cancer through a 
bench-to-population framework, synthesizing evidence on strategies for returning genomic results, facilitating 
cascade testing, and addressing ethical, legal, social, and implementation challenges. We highlight the complexity 
of communicating genomic risk, managing uncertain and secondary findings, and ensuring informed consent in 
population-level contexts. Persistent barriers to cascade testing uptake, including reliance on proband-mediated 
communication, health system constraints, socioeconomic inequities, and cultural factors, are examined alongside 
emerging interventions and quality-improvement frameworks. Drawing on international case studies and national 
pilot programs, we assess health system readiness across infrastructure, workforce capacity, data governance, 
reimbursement, and policy environments. Finally, we identify key research priorities and future directions to 
support equitable, scalable, and sustainable population genomics initiatives. Integrating return-of-results 
strategies, cascade testing, and health system preparedness is essential to realizing the public health potential of 
population genomics for breast cancer prevention while minimizing harm and exacerbation of existing health 
inequities.