Why BRCA Testing

Mutations in BRCA1 or BRCA2 cause Hereditary Breast and Ovarian Syndrome (HBOC). Now mutations in the BRCA1 and BRCA2 genes provide an indication for treatment with the PARP inhibitors Lynparza® (olaparib), Talzenna® (talazoparib) and Rubraca® (rucaparib).

Normally, the proteins produced by the BRCA1 and BRCA2 genes prevent cells from developing into cancer by aiding in the repair of mutations in other genes through a process known as double-stranded DNA repair. When one of these genes becomes ineffective due to a deleterious mutation, the cell can no longer perform double-stranded repair DNA and are homologous recombination deficient. HR deficiency can increase the risk for cancer, but is also a biomarker for certain targeted therapies to treat cancer when it develops

Cancer Cell

Cancer cells with a germline BRCA1/2 mutation are more susceptible to treatments that directly or indirectly damage DNA such as PARP inhibitor therapy or DNA damaging chemotherapy. Identifying your patients with a BRCA1/2 mutation makes it possible to utilize targeted therapy to more precisely identify and attack cancer cells. Testing for BRCA1/2 allows therapy to be personalized based on the biology of a patient. 1-3

Sources:

  1. Robson et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med (2018). 377:523-533.
  2. Litton et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA mutation. N Engl J Med 2018;379:753-63.
  3. Moore et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med (2018). DOI: 10.1056/NEJMoa1810858.