title: Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature.
abstract: BACKGROUND
  overexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.
  
  
  METHODS
  in all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.
  
  
  RESULTS
  in the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.
  
  
  CONCLUSIONS
  the 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome.
authors.affiliation: Division of Diagnostic Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam NL-1066CX, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Knauer
authors.forename: F
authors.initials: F
authors.lastname: Cardoso
authors.forename: J
authors.initials: J
authors.lastname: Wesseling
authors.forename: P L
authors.initials: PL
authors.lastname: Bedard
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
authors.forename: E J T
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: L J
authors.initials: LJ
authors.lastname: van 't Veer
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human