Novel Treatment BRCA Mutated Metastatic Breast Cancer
Up to 10% of breast cancers are caused by inherited mutations BRCA 1 and BRCA 2. BRCA 1 and 2 play a major role in repairing DNA double strand breaks.
BRCA 1 and 2 mutations give a lifetime risk of developing breast cancer between 50-80%.
A new class of drugs called PARP inhibitors (poly ADP-ribose polymerase) work by disabling the tumor cell ability to repair its damaged DNA leading to cell death.
The PARP inhibitor olaparib FDA approved as single agent for BRCA positive ovarian cancer has currently shown promising results in phase III trials for metastatic BRCA positive breast cancer and is under review for FDA approval. Olaparib is an oral drug well tolerated with few side effects including nausea, fatigue, joint pain serious but uncommon side effects include MDS, lung inflammation and AML.
Another PARP inhibitor currently being tested in metastatic BRCA positive breast cancer is veliparib, which is in phase III trial in combination with carboplatin and paclitaxel.
Rucaparib, niraparib and talazoparib are also currently being tested in various phase II and phase III trials for metastatic BRCA positive breast cancer.
Because PARP inhibitors target cells that have acquired at least one defect in a DNA repair pathway the next approach taken is to study their efficacy in the preventive setting as well as the adjuvant setting, very intriguing prospective.