title: Effective tamoxifen therapy of breast cancer involves both antiproliferative and pro-apoptotic changes.
abstract: 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.
authors.affiliation: ICRF Medical Oncology Unit, Western General Hospital, Crewe Road South, Edinburgh, UK. david.cameron@ed.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Cameron
authors.forename: J C
authors.initials: JC
authors.lastname: Keen
authors.forename: J M
authors.initials: JM
authors.lastname: Dixon
authors.forename: C
authors.initials: C
authors.lastname: Bellamy
authors.forename: A
authors.initials: A
authors.lastname: Hanby
authors.forename: T J
authors.initials: TJ
authors.lastname: Anderson
authors.forename: W R
authors.initials: WR
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen; D004250:DNA Topoisomerases, Type II