title: Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.
abstract: OBJECTIVE
  To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients.
  
  
  METHODS
  HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained.
  
  
  RESULTS
  HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size.
  
  
  CONCLUSIONS
  Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients.
authors.affiliation: Department of Haematology, Flinders Medical Centre, Bedford Park, South Australia.
authors.forename: R
authors.initials: R
authors.lastname: Seshadri
authors.forename: F A
authors.initials: FA
authors.lastname: Firgaira
authors.forename: D J
authors.initials: DJ
authors.lastname: Horsfall
authors.forename: K
authors.initials: K
authors.lastname: McCaul
authors.forename: V
authors.initials: V
authors.lastname: Setlur
authors.forename: P
authors.initials: P
authors.lastname: Kitchen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012044:Regression Analysis; D016019:Survival Analysis
chemical_list: D009856:Oncogene Proteins, Viral; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone