We found a twofold and threefold increased risk of breast cancer for the women with MSH6 and PMS2 PVs in our cohort, whereas no breast cancer association was observed for MLH1 or MSH2. PVs in MSH6 and PMS2 were found to confer 31.1% and 37.7% cumulative risks for breast cancer by the age of 60 while PVs in MLH1 or MSH2 were found to confer breast cancer risks close to the expected general population risk, 16.1% and 15.5%, respectively. Here, MSH6 is linked to breast cancer.