Effects of nonsteroidal antiestrogens, analog II and tamoxifen, on a metastatic transplantable rat mammary tumor.

This study was designed to determine whether treatment with the nonsteroidal antiestrogens analog II and tamoxifen given three times per week, 2 weeks before and 2 weeks after tumor cell transplantation, influenced the metastasis of a transplantable, metastatic rat mammary tumor, DMBA-4. Following transplantation of 2,000 viable tumor cells into the fifth and sixth mammary fat pads of 50-day-old inbred, female WF rats, all rats in all 3 groups displayed primary tumors by 5 weeks post tumor transplant. Analog II delayed the primary tumor development when compared to the time of the primary tumor development in either the control (untreated) or tamoxifen-treated groups. No metastatic tumors were found in the analog II-treated group 5 weeks after tumor transplantation, and only 1 animal in the tamoxifen-treated group had a secondary tumor, whereas 50% of the control animals had metastatic tumors. Six weeks after tumor implantation, palpable secondary tumors had developed in 40% of the analog II-treated group and 80% of the tamoxifen-treated group, whereas 60% of the control animals had developed secondary tumors. By the end of the study (7 wk) no differences existed between primary or secondary tumor incidences or between control and antiestrogen-treated groups. Both antiestrogens were effective in delaying the development of secondary tumors, especially during the time of treatment. Following cessation of treatment, analog II prevented metastatic tumor development for up to a month and tamoxifen, for 3 weeks. Further studies are indicated to determine if continuous treatment can effectively inhibit metastatic tumor development indefinitely.