title: Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer.
abstract: BACKGROUND
  Previous reports based on small patient numbers suggested that changes in serum HER-2/neu levels may predict response or lack of response to trastuzumab-based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER-2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff.
  
  
  METHODS
  This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first-line trastuzumab-based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER-2/neu decrease >or=20% (receiver operating curve analysis) was defined as a significant HER-2/neu change.
  
  
  RESULTS
  Of the 307 patients with MBC, 191 patients (62%) had a significant decline (>20%) in serum HER-2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER-2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER-2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P < .0001), longer duration of response (369 days vs 230 days; P = .008), and longer overall survival (898 days vs 593 days; P < .018).
  
  
  CONCLUSIONS
  In this pooled analysis of 307 patients with MBC, individuals who did not achieve a significant decline (>or=20%) in serum HER-2/neu levels had decreased benefit from trastuzumab-based therapy, and these patients should be considered for clinical trials evaluating additional HER-2/neu-targeted interventions.
authors.affiliation: Department of Hematology-Oncology, Penn State Hershey Cancer Center, Penn State University/Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
authors.forename: Suhail M
authors.initials: SM
authors.lastname: Ali
authors.forename: Walter P
authors.initials: WP
authors.lastname: Carney
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lotz
authors.forename: Diana
authors.initials: D
authors.lastname: Luftner
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Pichon
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab