Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer

Br J Cancer. 2001 Oct 19;85(8):1106-12. doi: 10.1054/bjoc.2001.2048.


The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis*
  • Middle Aged
  • Multivariate Analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Receptors, Estrogen / analysis
  • Survival Rate
  • Tumor Suppressor Protein p53 / analysis


  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Tumor Suppressor Protein p53