title: Pertuzumab : evolving therapeutic strategies in the management of HER2-overexpressing breast cancer.
abstract: BACKGROUND
  HER2 overexpression or amplification is present in approximately one-fifth of breast cancers and historically was associated with aggressive disease and poorer prognosis. The introduction of the humanized monoclonal antibody trastuzumab dramatically improved disease-free survival (DFS) and overall survival (OS) in this subgroup. As the majority of patients with metastatic disease ultimately develop resistance to trastuzumab, a need exists for more effective targeted therapies. Pertuzumab is an anti-HER2/neu-targeted therapy in the late stages of clinical development. The combination of pertuzumab, trastuzumab and docetaxel has been found to have an OS benefit in patients with HER2 positive metastatic breast cancer (MBC) when used in the first-line setting. This reflects a new standard of care, and pertuzumab was recently approved for this indication by the Food and Drug Administration (FDA). The efficacy of pertuzumab and trastuzumab in conjunction with chemotherapy is currently being evaluated in the adjuvant setting.
  
  
  METHODS
  This article provides an overview of preclinical investigations in addition to reviewing pertinent Phase I, Phase II and Phase III clinical trials.
  
  
  CONCLUSIONS
  Pertuzumab, in combination with the humanized monoclonal antibody trastuzumab, and docetaxel is a standard of care for patients with previously untreated metastatic breast cancer based on the CLEOPATRA study showing a survival benefit. There is no increase in cardiac toxicity with the combined HER2-targeted therapy. Future issues will address appropriate sequencing and combination with other anti-HER2-targeted therapies and/or chemotherapy.
authors.affiliation: Medical Oncology Branch, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ciara C
authors.initials: CC
authors.lastname: O'Sullivan
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020360:Neoadjuvant Therapy; D011358:Product Surveillance, Postmarketing; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C485206:pertuzumab