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The novel anti-oestrogen idoxifene inhibits the growth of human MCF-7 breast cancer xenografts and reduces the frequency of acquired anti-oestrogen resistance.

Abstract
The effect of idoxifene, a novel anti-oestrogen with less agonist activity than tamoxifen, was compared with that of tamoxifen on the growth of hormone-dependent MCF-7 breast cancer xenografts. Forty tumours were established with oestradiol support in ovariectomized athymic mice, allowed to grow to a median volume of 420 mm3 and then continued with oestradiol, no support, tamoxifen or idoxifene delivered by 1.5-cm silastic capsule. Tumour regression occurred with both anti-oestrogens, although maximum regression was observed following oestradiol withdrawal alone. While prolonged anti-oestrogen therapy was associated with static growth, tumour volumes were significantly lower with idoxifene (P=0.01). After 6 months, 0/10 idoxifene-treated tumours developed acquired resistance compared with 3/10 tumours treated with tamoxifen. In separate experiments, 94 animals were treated initially with oestradiol, tamoxifen, idoxifene or placebo following implantation with 1-mm3 pieces of either wild-type (WT) or tamoxifen-resistant (TR) MCF-7 tumour. After 4 months, only 1/11 WT tumours became established with idoxifene compared with 4/11 with tamoxifen, 8/12 with oestradiol and 0/12 with placebo. Likewise, fewer TR tumours were supported by idoxifene (3/12) than by tamoxifen (8/12) or oestrogen (11/12). These data indicate that, compared with tamoxifen, idoxifene shows reduced growth support of MCF-7 xenografts and may share only partial cross-resistance. Furthermore, the development of acquired anti-oestrogen resistance may be reduced during long-term idoxifene therapy. The drug's reduced agonist activity may, in part, explain these observations and indicate a preferable biochemical profile for breast cancer treatment.
AuthorsS R Johnston, S Riddler, B P Haynes, R A'Hern, I E Smith, M Jarman, M Dowsett
JournalBritish journal of cancer (Br J Cancer) Vol. 75 Issue 6 Pg. 804-9 ( 1997) ISSN: 0007-0920 [Print] England
PMID9062399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Estrogen Antagonists
  • Tamoxifen
  • idoxifene
  • Estradiol
Topics
  • Animals
  • Breast Neoplasms (blood, prevention & control)
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Estradiol (pharmacology)
  • Estrogen Antagonists (blood, therapeutic use)
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Hormone-Dependent (blood, prevention & control)
  • Tamoxifen (analogs & derivatives, blood, therapeutic use)

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