Abstract

Polygenic risk scores (PRS) have emerged as promising tools for stratifying breast cancer risk and informing 
screening and prevention strategies. However, their clinical utility in African ancestry populations remains limited 
due to poor transferability, miscalibration, and uncertainty surrounding appropriate decision thresholds. Most 
existing PRS are derived from genome-wide association studies (GWAS) conducted predominantly in European 
ancestry populations, resulting in reduced predictive accuracy and systematic over- or underestimation of risk 
when applied to individuals of African ancestry. This review examines the current evidence on the transferability 
of breast cancer PRS to African ancestry populations, with particular emphasis on population-specific genetic 
architecture, methodological challenges, calibration performance, and threshold derivation strategies. Empirical 
findings consistently demonstrate diminished predictive performance and substantial miscalibration of European
derived PRS in African ancestry cohorts, raising concerns for equitable clinical implementation. We further 
explore calibration methods, decision-curve analysis, and ancestry-sensitive thresholding approaches, highlighting 
their implications for risk stratification, screening eligibility, and preventive interventions. Finally, we identify key 
evidence gaps, including underrepresentation in GWAS, limited biobank infrastructure, and heterogeneity in 
phenotype definitions, and propose future directions emphasizing multi-ancestry GWAS, integrative multi-omics 
models, standardized reporting, and equity-centered implementation frameworks. Addressing these challenges is 
essential to ensure that PRS-based breast cancer risk prediction contributes meaningfully and ethically to 
precision medicine for African ancestry populations.