BRCA1 and breast cancer: At the time of their discovery, the BC predisposition genes BRCA1 and BRCA2 fitted nicely into the tumor suppressor gene (TSG) model designed by Knudson13 and Comings.14 Indeed, an inherited heterozygous mutation in BRCA19 or BRCA210 (mostly a protein truncating mutation) is responsible for the increased BC risk in the family.