ABSTRACT
Triple negative breast cancer (TNBC) lacks expression of the estrogen and progesterone receptors and lacks over-expression or amplifi cation of the HER2 oncogene, and therefore is non-responsive to clinical treatments targeting either the estrogen receptor, estrogen production or the Her2protein. TNBCs are aggressive cancers associated with a poor prognosis (Anders et al. 2010). TNBC, basal-like, and BRCA-mutated breast cancers share many molecular and pathologic characteristics, and TNBCs often have HR defects (Anders et al. 2010). Further, TNBC in patients without BRCA mutations may have epigenetic silencing of BRCA1 by promoter methylation or have other defects elsewhere in the HR pathway (Wei et al. 2008; Annunziata and O’Shaughnessy 2010). Because of this “BRCAness” of TNBC, researchers are investigating the use of PARP inhibitors in their treatment. Preclinical studies established that basal-like breast cancer and TNBC cell lines are sensitive to PARP inhibitors, which may be due to defective HR or SSBR (Alli et al. 2009). A phase II study treated TNBC patients with gemcitabine and carboplatin with or without the PARP inhibitor iniparib: patients receiving iniparib displayed signifi cantlyimproved progression free and overall survival (O’Shaughnessy et al. 2011).
