title: Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189.
abstract: OBJECTIVE
  The identification of a subset of patients with axillary lymph node-positive breast cancer with an improved prognosis would be clinically useful. We report the prognostic importance of histologic grading and proliferative activity in a cohort of patients with axillary lymph node-positive breast cancer and compare these parameters with other established prognostic factors.
  
  
  METHODS
  This Eastern Cooperative Oncology Group laboratory companion study (E4189) centered on 560 axillary lymph node-positive patients registered onto one of six eligible clinical protocols. Flow cytometric (ploidy and S-phase fraction [SPF]) and histopathologic analyses (Nottingham Combined Histologic Grade and mitotic index) were performed on paraffin-embedded tissue from 368 patients.
  
  
  RESULTS
  Disease recurred in 208 patients; in 161 (77%), within the first 5 years. Mitotic index and grade were associated with both ploidy and SPF (P </=.01). Within the first 5 years of follow-up, mitotic index (P =.004), grade (P =.004), ploidy (P =. 006), and SPF (P =.05) were associated with time to recurrence; there was also a significant association with survival. The effect of mitotic index was largely a result of the difference between 0 to 2 mitoses/10 high-power fields (HPF; 5-year recurrence of 31%) and more than 2 mitoses/10 HPF (5-year recurrence of 52%). The 0 to 2 mitoses/10 HPF group was independently associated with improved prognosis at 5 years (P =.002) in regression models that included other standard prognostic factors.
  
  
  CONCLUSIONS
  A subset of axillary lymph node-positive patients with improved prognosis may be identified using a lower (< 3 mitoses/10 HPF) mitotic count than is usually performed.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Simpson
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.forename: L G
authors.initials: LG
authors.lastname: Dressler
authors.forename: C D
authors.initials: CD
authors.lastname: Cobau
authors.forename: C I
authors.initials: CI
authors.lastname: Falkson
authors.forename: K W
authors.initials: KW
authors.lastname: Gilchrist
authors.forename: K J
authors.initials: KJ
authors.lastname: Pandya
authors.forename: D L
authors.initials: DL
authors.lastname: Page
authors.forename: N J
authors.initials: NJ
authors.lastname: Robert
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016013:Likelihood Functions; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008938:Mitosis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis