Gao C, Polley EC, Hart SN, et al. - Researchers aimed at determining the joint correlation of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. From predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium, they evaluated a total of 26,798 non-Hispanic white BC cases and 26,127 controls for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. They used effect estimates from BC genome-wide association studies to create PRS based on 105 common variants; evaluation in the performance of an overall BC PRS and estrogen receptor–specific PRS was done. Among carriers of PVs in moderate penetrance genes such as CHEK2 and ATM, PRS showed particular importance of risk stratification. Carriers of BRCA1 or BRCA2 were at smaller risks linked with modification in PRS but there was no other effect modification by PRS for carriers of PVs in the other genes tested. Overall PRS provided a relevant risk gradient among both carriers and noncarriers of PVs in BC predisposition genes and may be particularly relevant for women with PVs in ATM and CHEK2. They suggest incorporation of PRS into risk prediction models as possibly helpful for determining the potential benefit of breast magnetic resonance imaging and the age of BC screening initiation.