Abstract
Toremifene is a nonsteroidal antiestrogen currently being evaluated for the treatment of breast cancer. Toremifene (10-10-10-6 M) inhibited the growth of MCF-7 breast cancer cells in vitro but was ineffective against hormone-independent MDA-MB-231 cells. This activity was reproduced in vivo using the athymic mouse model. Maximal MCF-7 tumor growth was produced in athymic mice by circulating estradiol levels of approximately 200 pg/ml (from a 0.5 cm silastic capsule implanted sc). Toremifene (77 ± 44 μg/day from a 2 cm silastic capsule) inhibited estradiol (0.5 cm capsule)-stimulated growth by more than 70%. No tumor growth was observed in mice treated with toremifene alone, although toremifene acted as a weak partial agonist and potent antagonist on the mouse uterus. The growth of MDA-MB-231 tumors was not influenced by either estradiol or toremifene. Toremifene (200 μg/day) was effective in preventing the development of 7,12-dimethylbenzanthracene-induced rat mammary tumors when given po from day 28 after carcinogen administration. The antitumor activity was reversed if the toremifene was stopped. These findings indicate toremifene is a tumoristatic agent rather than a tumoricidal agent. Clinical trials with toremifene should employ an indefinite treatment strategy to control tumor recurrence in adjuvant studies.
Original language | English (US) |
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Pages (from-to) | S |
Journal | Breast Cancer Research and Treatment |
Volume | 16 |
Issue number | 1 Supplement |
DOIs | |
State | Published - Aug 1990 |
Externally published | Yes |
Keywords
- DMBA-induced tumors
- antiestrogen
- athymic mice
- drug metabolism
ASJC Scopus subject areas
- Oncology
- Cancer Research