title: Emerging drugs targeting human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer.
abstract: BACKGROUND
  Human epidermal growth factor 2 (HER2) overexpression is present in 20% of breast cancer patients. It is associated with more aggressive disease and worse clinical outcome. New drugs are thus needed. Approved and future treatments will be discussed in this review.
  
  
  METHODS
  The monoclonal antibodies trastuzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib and the antibody-drug conjugate trastuzmab emtansine are approved for HER2 positive breast cancer. The combination of trastuzumab, pertuzumab and docetaxel is currently the first-line treatment in the metastatic setting. New therapies are still needed due to frequent relapse and resistance. These include mammalian target of rapamycin inhibitors, heat shock protein 90 inhibitors, pan-HER2 tyrosine kinase inhibitors, antibody-drug conjugates, immunotherapy agents (antibodies and vaccines), radioimmunotherapy and HER2 specific affinity proteins. Possible developmental issues are the complexity of the molecular biology of the HER2 positive cancer cell, the occurrence of resistance, toxicity and the high cost.
  
  
  CONCLUSIONS
  The determination of the right sequence of use of old and new therapies remains a challenging issue. The selection of patients who do or don't benefit from potentially toxic chemotherapy is also difficult. Central nervous system metastases are a common problem in HER2 positive breast cancer that needs to be addressed in future trials.
authors.affiliation: a Internal Medicine , Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel , Brussels , Belgium.
authors.forename: Gil
authors.initials: G
authors.lastname: Awada
authors.affiliation: b Medical Oncology Clinic , Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gombos
authors.affiliation: b Medical Oncology Clinic , Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Aftimos
authors.affiliation: b Medical Oncology Clinic , Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2; antibody drug conjugates; breast cancer; monoclonal antibodies; tyrosine kinase inhibitors