Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare.
When T-47D human breast cancer cells were grown in medium supplemented with foetal calf serum (FCS) which had been depleted of endogenous oestradiol (E2) by dextran-charcoal treatment (CS-FCS) tamoxifen and E2 had biphasic effects on cellular proliferation. At lower concentrations E2 and, to a lesser extent, tamoxifen stimulated cell proliferation, with maximal effect at 10(-9) M, and with corresponding increases in the % S phase cells; this was not seen with medium containing untreated FCS. At higher doses tamoxifen (1-1.5 X 10(-5) M) and E2 (1.5 X 10(-5) M) in the presence of CS-FCS inhibited cell proliferation. These observations may explain features of the clinical phenomenon of tamoxifen-induced tumour flare: tamoxifen may temporarily exert a weak oestrogen agonist activity on the tumour as its concentration gradually increases after initiation of treatment; further, patients with tamoxifen-induced tumour flare often experience a remission with continued administration of the drug, presumably as the intratumour concentration of tamoxifen continues to accumulate to an inhibitory level.
D001943:Breast Neoplasms / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007399:Interphase / Q000187:drug effects; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D013629:Tamoxifen; D004958:Estradiol