title: HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial.
abstract: OBJECTIVE
  We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial.
  
  
  METHODS
  All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103).
  
  
  RESULTS
  Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P < .0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P < .006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively.
  
  
  CONCLUSIONS
  These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.
authors.affiliation: Serene M. and Frances C. Durling Professor of Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Monica M
authors.initials: MM
authors.lastname: Reinholz
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Tenner
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schroeder
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007753:Laboratories; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010338:Pathology, Clinical; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab