Pertuzumab in Metastatic Breast Cancer

The human epidermal growth factor family of receptors (HER1/EGFR, HER2, HER3, and HER4) plays an important role in the proliferation, differentiation, and transformation of tumor cells (Gianni et al., 2010). The receptors are highly expressed in many solid tumor types, including breast cancer. Approximately 15% to 30% of breast cancers overproduce the growth-promoting protein HER2/neu. These tumors tend to grow fast and are generally more likely to recur than tumors that do not overproduce HER2. The introduction of the humanized monoclonal antibody trastuzumab (Herceptin), which suppresses HER2mediated signaling by binding to the extracellular domain of the HER2 protein, has dramatically improved outcomes for patients with HER2-positive breast cancer and changed the natural course of HER2-positive disease (Baselga et al., 2012). However, as most patients with HER2-positive metastatic breast cancer will eventually progress on trastuzumab regimens, additional interventions will be required to extend the life expectancy of these patients. Dual antibody therapy targeted toward HER2 represents an important treatment option.