title: Dual human epidermal growth factor receptor 2 blockade:  another step forward in treating patients with human epidermal growth factor receptor 2-positive breast cancer.
abstract: OBJECTIVE
  Many antihuman epidermal growth factor receptor (anti-HER2)-targeted agents, covering a broad spectrum of mechanisms of action, have been recently developed. The concept of dual anti-HER2 blockade has been preclinically and clinically assessed with positive results. In this article, the authors review the biologic rationale for dual HER2 blockade, along with the clinical findings.
  
  
  RESULTS
  Dual anti-HER2 blockade has been assessed in the metastatic setting, including with chemotherapy-free regimens, leading to impressive responses, even in heavily pretreated patients. In the neoadjuvant setting, dual anti-HER2 blockade combinations and chemotherapy have almost doubled the rates of pathologic complete response compared to single anti-HER2 therapy. Similar strategies are now actively being pursued in the adjuvant setting and, it is hoped, will improve the outcome of many patients with HER2-positive breast cancer.
  
  
  CONCLUSIONS
  Combining different anti-HER2-targeted agents represents a promising therapeutic strategy, now reaching clinical practice. There are major clinical challenges yet to be resolved, rising from the increasing number of potential combinations and their mechanisms of resistance. Smartly designed clinical trials are required to address these challenges and perhaps to define a subset of patients that can be spared chemotherapy.
authors.affiliation: Institut Jules Bordet, l'Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zardavas
authors.forename: Ivana
authors.initials: I
authors.lastname: Bozovic-Spasojevic
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
mesh_terms: D000077716:Afatinib; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D000077341:Lapatinib; D058990:Molecular Targeted Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000068878:Trastuzumab
chemical_list: D000077716:Afatinib; D061067:Antibodies, Monoclonal, Humanized; D000077341:Lapatinib; D011799:Quinazolines; D011804:Quinolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C487932:neratinib