POLE and breast cancer: This paradigm is particularly pronounced in familial cancers with known germline mutations of high penetrance in DNA repair genes, e.g., breast cancer 1 and 2 (BRCA1 and 2) mutations in breast cancer; MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), PMS1 homolog 2 (PMS2), and DNA polymerase epsilon (POLE) mutations linked to mismatch repair or polymerase deficiency in colorectal and ovarian cancers; RAD51 paralog C and paralog D (RAD51C and D) deleterious mutations and BRCA1 mutation in OvC [6,7,8,9].