Experimental Therapeutics for the Treatment of Triple Negative Breast Cancer

Abstract

Triple negative breast cancers (TNBCs) are defined as tumors that do not express the estrogen receptor (ER), the progesterone receptor (PR) and the HER2 isoform of the epidermal growth factor receptor (EGFR)(Foulkes et al., 2010). They account for approximately 10-17% of all breast cancers (Reis-Filho & Tutt, 2008). Clinically, they are more prevalent among young African and African-American women (Reis-Filho & Tutt, 2008). TNBCs are poorly differentiated, highly malignant, more aggressive and have a poor outcome (Chen & Russo, 2009). They are also characterized by early recurrence and a high rate of visceral metastasis (Conte & Guarneri, 2009). Moreover, the peak risk of recurrence occurs within three years of diagnosis and the mortality rates are increased for five years after diagnosis (Kwan et al., 2009). The molecular changes associated with TNBCs have been characterized by various immunohistochemistry and gene expression profiling studies. Specifically, they include p53 mutation, overexpression of Ki67 and EGFR, and dysfunction in the BRCA1 pathway (Rowe et al., 2009). It is estimated that EGFR is expressed in 60% of TNBCs (Arslan et al., 2009). In addition, TNBCs have an over expression of cytokeratins 5, 6, 14, and 17, smooth muscle actin, P-cadherin and c-kit (Irvin & Carey, 2008, Venkitaraman, 2010).