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Cancer Res. 1987 Aug 1;47(15):4020-4.

Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model.


We have compared the antitumor activities of the antiestrogens, keoxifene (LY 156758) and tamoxifen (TAM), using the N-nitrosomethylurea (NMU) rat mammary carcinoma model. To establish an effective antitumor dose of TAM in this model, rats were treated 2 wk after initiation with NMU for 8 wk with s.c. daily injections of 6.25 micrograms, 25 micrograms, or 100 micrograms of TAM in peanut oil. At the 25-micrograms and 100-micrograms daily doses, TAM completely inhibited tumor appearance during the therapy period. An effective antitumor dose of TAM (100 micrograms daily) was compared to 20-, 100-, or 500-micrograms daily doses of keoxifene 7 wk after NMU initiation. None of the keoxifene-treated groups prevented the appearance of tumors as effectively as TAM during 13 wk of therapy. When keoxifene was compared to TAM at equivalent daily doses of 100 and 500 micrograms daily starting 2 wk after NMU injection, the keoxifene groups again failed to prevent the appearance of all tumors during 10 wk of therapy. TAM, however, completely suppressed any tumor formation. In the same experiment, animals treated with 500 micrograms of TAM had therapy stopped after 10 wk, and tumors started to appear 6 wk later. No tumors appeared when animals (n = 25) were treated continuously for 23 wk with 100 micrograms of TAM. In separate experiments, keoxifene (500 micrograms daily) and TAM (500 micrograms and 100 micrograms daily) administered for 1 wk blocked the binding of [3H]-estradiol in NMU tumors and in uteri. The effect lasted for up to 5 wk after antiestrogen therapy was stopped. These experiments demonstrate that keoxifene is not as effective in its antitumor action as TAM in the NMU model.

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