Breast Cancer patients with germline Breast Cancer Gene (BRCA) mutations have a greater advantage from targeted therapy with Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi). The identification of patients with homologous recombination deficiency (HRD) tumors that may be sensitive to PARPi besides those with germline BRCA1/2 mutations remains an important point of research. There is increasing evidence demonstrating that breast tumors with BRCAness may benefit from PARPi and there are studies ongoing to identify those subtypes which may benefit the most. Pancreatic cancer with HRD non-BRCA mutations seem to have very little benefit from PARPi, but in HRD non-BRCA ovarian and prostate cancer, PARP inhibition appears to be a reasonable therapeutic target. Also, there is data showing that genomic instability caused by mutations in HRD genes, potentially makes cancer cells susceptible to chemotherapeutic drugs, such as anthracyclines or platinum salts. Widespread use of next generation sequencing could increase the role of hallmarks influencing the DNA repair system and therefore increase the therapeutic possibilities for cancer patients. In this review we evaluate the latest advances with PARPi in BRCAness Breast Cancer patients.

Breast cancer, BRCA mutations, HRD, BRCAness, PARP inhibitors