title: Systemic treatment of HER2-positive metastatic breast cancer: a systematic review.
abstract: OBJECTIVE
  We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2-positive metastatic breast cancer.
  
  
  METHODS
  We reviewed phase 2 and 3 studies in which an anti-HER2 agent was used in one or both arms of the study. While formal meta-analysis was not possible for such a heterogeneous group of trials, resulting forest plots outline some generalizable findings.
  
  
  RESULTS
  There is strong evidence that the addition of an anti-HER2 agent to standard chemo- or endocrine therapy improves clinically relevant measurable outcomes. There is also consistent evidence that initial treatment with trastuzumab alone (and subsequent use of a cytotoxic) is inferior to the initial combination of trastuzumab plus chemotherapy, and that either T-DM1 or dual anti-HER2 agents are superior to single anti-HER2 agent regimens. There is no strong evidence that the use of more than one cytotoxic agent together with an anti-HER2 agent confers any benefit over a single cytotoxic, anti-HER2 combination.
  
  
  CONCLUSIONS
  This review provides a strong evidence base for current clinical practice with a discussion of treatment in the Australian setting.
authors.affiliation: Westmead Hospital, New South Wales, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wilcken
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zdenkowski
authors.forename: Michelle
authors.initials: M
authors.lastname: White
authors.forename: Ray
authors.initials: R
authors.lastname: Snyder
authors.forename: Ken
authors.initials: K
authors.lastname: Pittman
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Prudence
authors.initials: P
authors.lastname: Francis
authors.forename: Richard
authors.initials: R
authors.lastname: De Boer
authors.forename: Maree
authors.initials: M
authors.lastname: Colosimo
authors.forename: Sue
authors.initials: S
authors.lastname: Chua
authors.forename: Jacquie
authors.initials: J
authors.lastname: Chirgwin
authors.forename: Jane
authors.initials: J
authors.lastname: Beith
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: anti-HER2 agent; breast cancer; metastatic; review; systematic