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Tamoxifen (TAM) is the most common drug used in the treatment of breast cancer. Side effects have limited its use. Recently, O-desalkyl-O-desmethyltamoxifen (DO-DMT) and L-deacyl-O-desmethyltamoxifen (DO-LM2) have been developed as a more specific TAM metabolite that induces apoptosis in breast cancer cells and prolongs the survival of mice in a xenograft model. The aim of this study was to evaluate the in vivo antitumor effect of DO-DMT and DO-LM2 in an animal model of breast cancer. First, the in vitro antitumor activity of DO-DMT and DO-LM2 was evaluated in MCF-7 and ZR-75-1 cells. The cytotoxic activity of DO-DMT and DO-LM2 was not influenced by estrogen and/or progesterone receptors, cell cycle, and apoptotic induction. Both drugs had a higher cytotoxic activity than TAM and caused apoptosis in MCF-7 cells after 24 h and 48 h treatment. 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