Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare
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AbstractWhen 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 10−9M, 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 × 10−5M) and E2 (1.5 × 10−5M) 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.

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