The Present and Future of the Treatment of Hereditary Breast Cancer

Currently women that have a hereditary breast cancer predisposition face screening, chemoprevention, and risk-reducing surgery as options for preventing the disease. Bilateral preventive oophorectomy, combined with either MRI screening or a bilateral preventive mastectomy, can contribute considerably to a better life expectancy. Bilateral prophylactic mastectomy can reduce the risk of breast cancer by up to 95% in BRCA1/BRCA2 mutation carriers. There are two important works that must be considered seminal in the treatment of hereditary breast cancer mainly BRCA1/2 carriers. Wesierska-Gądek et al. have shown that using PARP inhibitors could be relevant in carriers of BRCA1\2 mutations based on the knowledge that BRCA1/2-mutant cells are hypersensitive to inactivation of poly(ADP-ribose) polymerase 1 (PARP-1). Another seminal paper published by Arun et al. in 2015 comparing three different PARP inhibitors such as the ABT-888 (Veliparib), BSI-201 (Iniparib), and AZD228 (Olaparib) demonstrated that they have anti-proliferative effects in breast cancer cell lines with BRCA1 or BRCA2 mutations. An interesting observation from this study was that AZD228 (Olaparib) was the most potent PARP inhibitor but only in those cells that have allelic loss.