title: Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients.
abstract: The introduction of trastuzumab in the treatment of HER-2-positive metastatic breast cancer patients favorably changed the natural history of this disease. First-line treatment with trastuzumab and taxanes demonstrated a significant improvement in overall survival and progression-free survival compared with taxane alone. Despite such a major advance, HER-2-positive metastatic breast cancer will eventually progress in most patients. Moreover chemotherapy-associated toxicities, such as myelosuppression (docetaxel) and neurotoxicity (paclitaxel), may hamper the possibility to adequately treat metastatic breast cancer and may have a negative effect on patients' quality of life. The need for more effective and better-tolerated therapy for HER-2-positive metastatic breast cancer led to the development of new anti-HER-2 agents. Pertuzumab and trastuzumab emtansine are two of the new agents that will change the approach to the treatment of HER-2-positive metastatic breast cancer. Pertuzumab is a humanized monoclonal antibody that binds HER-2 at a different epitope of the HER-2 extracellular domain (subdomain II) than that at which trastuzumab binds. Trastuzumab emtansine is a HER-2-targeted antibody-drug conjugate, composed of the cytotoxic microtubule polymerization inhibitor DM1 that is conjugated to the monoclonal antibody trastuzumab, able to selectively deliver a cytotoxic agent to HER-2-positive tumor cells. TDM-1 is superior and less toxic than lapatinib plus capecitabine in metastatic breast cancer patients previously treated with trastuzumab and taxanes, and its role as a first-line therapy is currently under investigation.
authors.affiliation: Department of Medical Oncology, IRCCS (Istituto di Ricovero & Cura a Carattere Scientifico)- AOU (Azienda Ospedaliera Universitaria) San Martino-IST (Istituto Nazionale per la Ricerca sul Cancro), Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bighin
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids