Prognostic relevance of mitotic activity in patients with node-negative breast cancer

Mod Pathol. 2003 Nov;16(11):1067-75. doi: 10.1097/01.MP.0000093625.20366.9D.


The prognostic relevance of mitotic activity was analyzed in a series of 306 patients with node-negative breast cancer treated with locoregional therapy alone, until early relapse. Mitotic activity was evaluated as the number of mitotic figures per 10 high-power fields (mitotic activity index) or per 1000 tumor cells (mitotic index). Counting was carried out blindly by two observers. A high correlation was observed between the two determinations (r(s) =.96, P <.001). For clinical analysis, three mitotic activity index subgroups (mitotic figures/field </= 9, 10-19 and more than 19, according to grading criteria) and three mitotic index subgroups (percentage of mitotic figures less than 0.10, 0.11-0.50 and more than 0.50, according to tertile criteria) were considered. No relation was observed between mitotic variables and 6-year disease-free survival, whereas distant disease-free survival was strongly related to mitotic figures per 10 fields (85%, 89% and 70%, P =.012) and to the percentage of mitotic figures out of a total 1000 tumor cells (87%, 86% and 75%, P =.017). Similarly, both mitotic indices were significantly related to 6-year overall survival (99%, 95% and 77%, P <.001, for mitotic figures per 10 fields and 99%, 93% and 82%, P <.001, for the percentage of mitotic figures). These findings were particularly evident in patients with tumors of 1-2 cm. In conclusion, a high number of mitotic figures is associated with a higher probability of developing distant metastases and a shorter survival. The critical point remains the standardization of the preanalytical and analytical steps within quality control programs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / physiopathology
  • Female
  • Humans
  • Likelihood Functions
  • Lymph Nodes / pathology*
  • Middle Aged
  • Mitotic Index*
  • Neoplasm Recurrence, Local
  • Prognosis
  • Reproducibility of Results
  • Survival Analysis