title: Use of pertuzumab for the treatment of HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  Targeting the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors has proven to be effective as a therapeutic strategy for HER type 2 (HER2)-positive breast cancer. Since resistance to trastuzumab occurs relatively frequently, particularly in the metastatic setting, novel anti-HER2 targeted therapies with complementary and/or synergistic mechanisms of action have been under development. Pertuzumab, a HER2-targeted monoclonal antibody that prevents HER2 dimerisation, is the first of a class of promising targeted agents for the treatment of HER2-positive breast cancer.
  
  
  METHODS
  A review of the biomedical literature published prior to February 2013 was conducted in English using PubMed. ClinicalTrials.gov was searched for appropriate clinical trials. The search terms used included breast neoplasm, pertuzumab, dimerisation, and HER2-positive. Abstracts of studies presented at the ASCO and ESMO Annual Meetings, and San Antonio Breast Cancer Symposium were also included.
  
  
  RESULTS
  Pertuzumab represents a novel anti-HER2 targeted therapy for HER2-positive breast cancers. In this article, we describe the mechanism of action of pertuzumab, as well as its drug development process and preclinical testing results. Based on the results of ancillary studies, dual inhibition using pertuzumab and trastuzumab was shown to be effective for the management of HER2-positive metastatic breast cancers pre-treated with trastuzumab-based therapy. For the first-line setting, the combination of both pertuzumab and trastuzumab with docetaxel (CLEOPATRA trial; clinical evaluation of pertuzumab and trastuzumab) has changed the paradigm of patient management.
  
  
  CONCLUSIONS
  Pertuzumab provided a more comprehensive inhibition of HER2-driven signalling pathways. When administered together with trastuzumab, pertuzumab represent a significant advancement for the treatment of HER2-positive metastatic breast cancer patients.
authors.affiliation: Medical Oncology Department, Vall d'Hebron Institute of Oncology, Vall D'Hebron University Hospital, Barcelona, Spain. ldmattos@ir.vhebron.net
authors.forename: Leticia
authors.initials: L
authors.lastname: De Mattos-Arruda
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab