Proliferative activity in primary breast carcinomas is a salient prognostic factor

Cancer. 2004 Feb 1;100(3):455-64. doi: 10.1002/cncr.11916.


Background: The goal of the current study was to investigate the prognostic impact of proliferative activity, together with the other classic clinicopathologic prognostic factors (tumor size, tumor grade, receptor status, ploidy, and lymph node status), in breast carcinoma by counting mitoses and evaluating S phase fraction (SPF) in fresh and frozen tumor samples.

Methods: From March 1, 1990, to July 1, 1999, a total of 1984 previously untreated invasive breast carcinoma samples were snap-frozen for flow cytometry.

Results: After multivariate analysis incorporating all classic prognostic factors, SPF combined with mitotic activity (i.e., proliferative activity) remained the sole prognostic factor in the lymph node-negative group; proliferative activity was accompanied by tumor size as a prognostic factor in patients with lymph node-positive disease and by lymph node status, lymphatic invasion, and receptor status in the overall population. The predictive value of proliferative activity was superior to that of the reference standards (classic prognostic predictors according to the guidelines of our institution [common oncology practice] and the St. Gallen classification). A review of the literature, focusing on series in which fresh material was used, allowed us to demonstrate that there is widespread agreement regarding the correlation between SPF and prognosis, even after multivariate analysis.

Conclusions: S phase fraction is a valuable predictor of survival and can confidently be assessed in approximately 80% of cases. In conjunction with mitotic activity, SPF should become a prognostic factor that is used in daily practice by oncologists for the management of breast carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Cell Division / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Mitotic Index
  • Neoplasm Staging
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • S Phase / physiology*
  • Sampling Studies
  • Survival Rate


  • Biomarkers, Tumor