Effective tamoxifen therapy of breast cancer involves both antiproliferative and pro-apoptotic changes

Eur J Cancer. 2000 May;36(7):845-51. doi: 10.1016/s0959-8049(00)00013-7.


Despite knowledge of oestrogen receptor status, it is not always possible to predict which breast cancers will respond to tamoxifen. We have previously reported that decreased expression of Bcl-2 and/or Ki-S1 were associated with tumour response to neo-adjuvant tamoxifen in 50 elderly women with oestrogen receptor (ER)-positive breast cancer. In this study, we confirm that the expression of Bcl-2 and Ki-S1 are surrogates for the frequency of apoptosis and mitosis respectively, within these untreated breast cancers, with an inverse relationship between Bcl-2 expression and the apoptotic index (P<0.05), and a positive relationship between Ki-S1 expression and the mitotic index (P<0.01). However, after 3 months' tamoxifen treatment these relationships were no longer apparent. Moreover, amongst the 27 tumours in which Bcl-2 expression was reduced during the 3 months' therapy, there was a significant correlation between the response to therapy and the increase in apoptosis (P<0.05), whereas in those tumours in which Bcl-2 did not fall with therapy, there was a significant correlation between response and the decrease in mitosis (P<0.05). These data suggest there are at least two mechanisms for effective tamoxifen therapy: increased apoptosis as a consequence of reduced Bcl-2 expression, and decreased proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Female
  • Humans
  • Immunohistochemistry
  • Mitosis / drug effects
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tamoxifen / therapeutic use*
  • Time Factors


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tamoxifen
  • DNA Topoisomerases, Type II