title: Intracellular patterns of Her-2/neu, ras, and ploidy abnormalities in primary human breast cancers predict postoperative clinical disease-free survival.
abstract: OBJECTIVE
  In an earlier study, the presence of aneuploidy, Her-2/neu overexpression, and ras overexpression in the same cells (triple-positive cells) was of prognostic significance (P < 0.015) in 91 patients with localized breast cancer (median follow up, 32 months). Here, we present results involving a larger group of patients with longer follow-up.
  
  
  METHODS
  Fixed cell suspensions prepared from primary tumors of 189 patients with early breast cancer were studied prospectively by multiparameter flow cytometry. Correlated intracellular fluorescence-based measurements of cell DNA content and Her-2/neu and ras protein were obtained on each of >2000 cells in each tumor. Intracellular combinations of abnormalities in these measurements were correlated with subsequent patient disease-free survival (DFS). Median time on study was 54 months (range, 7-128 months).
  
  
  RESULTS
  DFS of patients with > or = 5% triple-positive tumor cells was shorter than those who did not meet this criterion (P = 0.004). The difference remained statistically significant after accounting for nodal status, tumor size, and each of the component abnormalities (P = 0.006). Node-negative patients whose tumors had fewer than 2 abnormalities/cell had an especially favorable clinical course, with a 5-year DFS of 96% (lower confidence bound, 86%).
  
  
  CONCLUSIONS
  Patterns of accumulated intracellular molecular abnormalities in cells of primary human breast cancers are predictive for subsequent DFS independently of the abnormalities themselves taken individually.
authors.affiliation: Department of Human Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15212, USA. shakney@wpahs.org
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Shackney
authors.forename: Charles A
authors.initials: CA
authors.lastname: Smith
authors.forename: Agnese
authors.initials: A
authors.lastname: Pollice
authors.forename: Kathryn
authors.initials: K
authors.lastname: Brown
authors.forename: Roger
authors.initials: R
authors.lastname: Day
authors.forename: Thomas
authors.initials: T
authors.lastname: Julian
authors.forename: Jan F
authors.initials: JF
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D042541:Intracellular Space; D008198:Lymph Nodes / Q000473:pathology; D008408:Mastectomy; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D018631:ras Proteins / Q000032:analysis*
chemical_list: D004247:DNA; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins