Towards a more precise and individualized assessment of breast cancer risk.

Many clinically based models are available for breast cancer risk assessment; however, these models are not particularly useful at the individual level, despite being designed with that intent. There is, therefore, a significant need for improved, precise individualized risk assessment. In this Research Perspective, we highlight commonly used clinical risk assessment models and recent scientific advances to individualize risk assessment using precision biomarkers. Genome-wide association studies have identified >100 single nucleotide polymorphisms (SNPs) associated with breast cancer risk, and polygenic risk scores (PRS) have been developed by several groups using this information. The ability of a PRS to improve risk assessment is promising; however, validation in both genetically and ethnically diverse populations is needed. Additionally, novel classes of biomarkers, such as microRNAs, may capture clinically relevant information based on epigenetic regulation of gene expression. Our group has recently identified a circulating-microRNA signature predictive of long-term breast cancer in a prospective cohort of high-risk women. While progress has been made, the importance of accurate risk assessment cannot be understated. Precision risk assessment will identify those women at greatest risk of developing breast cancer, thus avoiding overtreatment of women at average risk and identifying the most appropriate candidates for chemoprevention or surgical prevention.