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Breast Cancer Research and Treatment

, Volume 32, Issue 1, pp 49–55 | Cite as

Mechanisms of tamoxifen resistance

  • C. Kent Osborne
  • Suzanne A. W. Fuqua
Article

Summary

Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to bestimulated by tamoxifen just as they are by estrogens. In both animal models and clinical specimens, we have found lower tamoxifen uptake and somewhat altered tamoxifen metabolism in resistant tumors, but neither appears to explain tamoxifen stimulation of the resistant tumors. Nor do estrogen receptor losses or mutations appear to explain this phenomenon, although altered expression of transcriptional variant forms of the receptor may well contribute. Pure steroidal antiestrogens such as ICI 182,780 are capable of reversing tamoxifen-stimulated as well as estrogen-stimulated growth of these resistant tumors, and are now in clinical trials for this purpose.

Key words

animal models antiestrogens estrogen receptor variants ICI 182,780 pure steroidal antiestrogens tamoxifen resistance 

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • C. Kent Osborne
    • 1
  • Suzanne A. W. Fuqua
    • 1
  1. 1.Department of Medicine, Division of Medical OncologyUniversity of Texas Health Science CenterSan AntonioUSA

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