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

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 neoadjuvant 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. (C) 2000 Elsevier Science Ltd. All rights reserved.