Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer: Commentary

摘要

The human epidermal growth factor receptor 2 (HER2) gene is amplified or overexpressed in 20-25% of human breast cancers . The HER2eu gene encodes a 185-kd transmem-brane glycoprotein receptor (HER2) that has intrinsic tyro-sine kinase activity and belongs to the epidermal growth factor receptor (EGFR) family. The EGFR (HER1, erbB1), HER2eu (erbB2), HER3 (erbB3), and HER4 (erbB4) are members of the erbB family of transmembrane tyrosine kinases. Except for HER2, binding of receptor-specific lig-ands to the ectodomain of EGFR, HER3, and HER4 results in the formation of homodimeric and heterodimeric kinase-active complexes into which HER2 is recruited as a preferred partner. Breast cancer patients with HER2 amplification/ overexpression have a worse survival. Trastuzumab (T) is a humanised monoclonal antibody developed to target the HER2 receptor. Binding with high affinity to the extracellular domain of HER2, trastuzumab inhibits the proliferation of tumour cells that overexpress HER2 through changing subsequent pathways. Trastuzumab has demonstrated synergistic action with several chemotherapy agents preclini-cally.