POLD1 and breast carcinoma: ATM pathogenic variants confer a moderate risk of breast cancer (two to fivefold), but are not associated with bilateral breast tumors.37,38 Available studies have been unable to quantify the postulated increased risk to CRC.39 The carrier of POLD1 p.Arg525Arg and ATM p.Ser2407* developed a very aggressive phenotype, including three metachronous early-onset breast tumors (ages 35–53) and a CRC at age 69, supporting a cumulative effect of the two variants.