Systemic Treatment Considerations for Women with BRCA1/2-Associated Breast Cancer

Abstract

Both BRCA1 and BRCA2 proteins play a role in DNA damage response, and their deficiency leads to chromosomal instability and carcinogenesis. Hereditary mutations in either of these genes increase strikingly the lifetime risk of breast and ovarian cancer and to a lesser extent the risk of males’ breast and prostate cancer and of pancreatic cancer. It is generally accepted that when treated by standard therapy, the prognosis of BRCA- mutated breast cancer patients is equivalent to that of patients with sporadic disease. Increased sensitivity of BRCA-associated breast cancer to DNA damaging chemotherapy, especially platinum compounds, was demonstrated in preclinical models and in clinical trials. However, definitive evidence that would justify their advancement to clinical practice is lacking. Inhibitors of poly (ADP-ribose) polymerase target BRCA-deficient cells specifically. Multiple clinical trials with these compounds are ongoing, although none made its way to clinical practice yet. Hopefully, ongoing clinical research would eventually result in better treatment and improved prognosis.