title: Can hormone "resistant" breast cancer cells be inappropriately stimulated by tamoxifen?
abstract: We propose that the molecular heterogeneity of ER in breast tumor cells characterized by the presence of mutant receptor forms generates the cellular heterogeneity evident when PR or DNA ploidy are analyzed in cell subpopulations. Furthermore, it is likely that cellular heterogeneity leads to the lack of uniformity in response to tamoxifen that we have described. We find that heterogeneity of PR and DNA ploidy reflects existence of mixed subpopulations of breast cancer cells that are substantially remodeled under the influence of tamoxifen. It appears likely that rather than being "resistant," different subset of cells can be inhibited or stimulated by tamoxifen, and their suppression or outgrowth alters the phenotype of the tumor. PR heterogeneity of solid tumors of patients may predict for such a mixed, and potentially dangerous, response to antiestrogen treatment. As we learn more about the heterogeneity of PR, ER, and other proteins in tumors, we may be able to recognize such lethal subpopulations, which the FCM immunoassay can simply and rapidly measure. Our data also suggest that the use of tamoxifen as a chemopreventant in women at high risk of developing breast cancer should be viewed with caution.
authors.affiliation: University of Colorado Health Sciences Center, Denver 80262.
authors.forename: K B
authors.initials: KB
authors.lastname: Horwitz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D006728:Hormones; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen