title: High circulating HER2 extracellular domain levels correlate with reduced efficacy of an aromatase inhibitor in hormone receptor-positive metastatic breast cancer: a confirmatory prospective study.
abstract: BACKGROUND
  In this specifically designed, prospective study, the authors addressed the predictive value of circulating levels of the extracellular domain (ECD) of HER2 in patients with metastatic breast cancer who were treated with letrozole.
  
  
  METHODS
  Two hundred twenty-six patients with hormone receptor-positive, metastatic breast cancer received letrozole (2.5 mg daily) until they developed either disease progression or unacceptable toxicity. Efficacy was measured primarily as the time to progression (TTP) and, secondarily, as the objective response rate (ORR) and overall survival. HER2 ECD levels were determined by using a sandwich enzyme HER2/neu immunoassay before letrozole treatment was initiated. Positive HER2 ECD status was correlated with treatment efficacy.
  
  
  RESULTS
  Forty-two patients (19%) had elevated HER2 ECD levels, which were associated with primary tumor HER2 expression (P < .001) but not with age, performance status, location, or number of metastatic sites. The median TTP was significantly shorter among patients who had elevated HER2 ECD compared with the median TTP among patients who had normal levels (4 months vs 14 months; P = .0004), and the ORR was lower in the group with elevated HER2 ECD levels (14% vs 30%; P < .036). Overall survival was significantly shorter among patients with elevated serum HER-2 ECD (P < .0005).
  
  
  CONCLUSIONS
  Elevated HER2 ECD concentrations predicted poorer outcomes in postmenopausal women with metastatic hormone receptor-positive breast cancer who were treated with aromatase inhibitors like letrozole.
authors.affiliation: M. D. Anderson Cancer Center Spain, Madrid, Spain. rcolomer@seom.org
authors.forename: Ramon
authors.initials: R
authors.lastname: Colomer
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Cussac
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Jose I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernández
authors.forename: Ignasi
authors.initials: I
authors.lastname: Tusquets
authors.forename: Miguel
authors.initials: M
authors.lastname: Gil
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.forename: Manuel
authors.initials: M
authors.lastname: Constenla
authors.forename: Montserrat
authors.initials: M
authors.lastname: Gilabert
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
mesh_terms: D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000077289:Letrozole; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000627:therapeutic use*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles