Breast cancer risk among cariers of pathogenic variants in predisposition genes varies by polygenic risk score

A study by the Cancer Risk Estimates Related to Susceptibility Consortium among 26,798 non-Hispanic white breast cancer patients and 26,127 controls, from predominantly population-based studies, evaluated the joint association of pathogenic variants (PVs) in breast cancer predisposition genes and polygenic risk score (PRS) with breast cancer risk. The study found that PRS facilitates personalization of BC risk among carriers of PVs. Incorporating PRS into BC risk estimation may help identify over 30% of CHEK2 carriers and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting that the addition of PRS may prevent overscreening and enable more personalized risk management approaches.