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Hormone ‘resistance’ in breast cancer: The role of normal and mutant steroid receptors

  • Chapter
Mammary Tumorigenesis and Malignant Progression

Part of the book series: Cancer Treatment and Research ((CTAR,volume 71))

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Abstract

Faithful expression of genetic information is lost in tumor cells due to the formation of spontaneous cell variants. In breast cancer, this evolution is marked by progression of tumors from hormone-dependent, through hormone-responsive, to hormone-resistant states. Many resistant tumors no longer express estrogen receptors (ERs) and progesterone receptors (PRs), and this may be the basis for their hormone resistance. However, half of all advanced breast cancers are receptor positive, yet they too fail to respond to antiestrogen therapy. Both the cellular heterogeneity that mark progression of the disease and the hormone resistance that characterize the end stages of the disease have been longstanding clinical problems that are slowly yielding to basic research focused both on solid tumors taken directly from patients and on breast cancer cell lines derived from such tumors. This chapter discusses how mutant ERs serve as one mechanism for development of resistance. A suggestion is made that subpopulations of tumor cells can be stimulated, rather than inhibited, by antiestrogens like tamoxifen. Our recent work with normal PRs, showing conditions in which progesterone antagonists, too, can have inappropriate, agonist-like effects, is also described. These PR models represent additional mechanisms that may explain the hormone-resistant state. It is suggested that many ‘resistant’ tumors are not simply ignoring the hormone antagonist treatment; instead, in these tumors, the hormone antagonist has become stimulatory rather than inhibitory.

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Authors
  1. Kathryn B. Horwitz
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Editors and Affiliations

  1. Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC, USA

    Robert B. Dickson  & Marc E. Lippman  & 

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Horwitz, K.B. (1994). Hormone ‘resistance’ in breast cancer: The role of normal and mutant steroid receptors. In: Dickson, R.B., Lippman, M.E. (eds) Mammary Tumorigenesis and Malignant Progression. Cancer Treatment and Research, vol 71. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2592-9_7

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  • DOI: https://doi.org/10.1007/978-1-4615-2592-9_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6109-1

  • Online ISBN: 978-1-4615-2592-9

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