The concept of applying PARP1 inhibitors to treat HR deficient cancers, such as breast cancers with familial BRCA1 or BRCA2 mutations, has largely been based on the assumption that drugs targeting PARP1 impair BER or SSB repair, therefore leading to the generation of massive DSBs in cells which cannot be fixed by defective HR repair machinery, eventually causing cell death by activating p53—a form of synthetic lethality. This evidence concerns the gene BRCA2 and breast carcinoma.