The Role of Polygenic Risk Scores in Breast Cancer Risk Stratification and Surveillance Among Women with Increased Familial Risk: A Systematic Review

Breast cancer remains one of the most common malignancies among women worldwide. Risk assessment strategies traditionally rely on a combination of clinical, demographic, and familial factors, as well as the identification of pathogenic variants in high-penetrance genes. However, a substantial proportion of women present with an increased familial risk of breast cancer despite the absence of identifiable monogenic pathogenic variants. In this context, polygenic risk scores (PRS), which aggregate the effect of multiple common genetic variants associated with breast cancer susceptibility, have emerged as a promising tool for refining individual risk estimation. PRS have the potential to complement existing risk prediction models by improving the stratification of women according to their likelihood of developing breast cancer. More accurate risk stratification may help identify women who could benefit from tailored prevention strategies and more intensive surveillance programs, such as earlier initiation of screening or the use of additional imaging modalities. Nevertheless, the extent to which PRS can meaningfully influence risk classification and surveillance decisions among women with increased familial risk remains uncertain, as the available evidence is dispersed across different types of studies, including risk prediction modeling studies and observational research. The aim of this systematic review is to analyze and synthesize the available evidence on the use of polygenic risk scores for breast cancer risk stratification and to explore their potential implications for surveillance strategies in women with increased familial risk. Specifically, this review will examine whether the incorporation of PRS into risk assessment models contributes to changes in risk classification and whether these changes may affect recommendations related to breast cancer surveillance. By systematically evaluating the current literature, this review seeks to provide a comprehensive overview of how PRS are currently used in the context of familial breast cancer risk assessment and to identify potential gaps in the evidence. The findings are expected to clarify the potential role of PRS in refining risk stratification and to inform future research and clinical discussions regarding the integration of polygenic risk information into breast cancer prevention and surveillance strategies.