Models and mechanisms of acquired antihormone resistance in breast cancer: Significant clinical progress despite limitations

Elizabeth E. Sweeney, Russell E. McDaniel, Philipp Y. Maximov, Ping Fan, V. Craig Jordan

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded signifi cant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75-1) that continue to advance our understanding of the estrogenregulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line, in particular, has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated fi ndings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer.

Original languageEnglish (US)
Pages (from-to)143-163
Number of pages21
JournalHormone Molecular Biology and Clinical Investigation
Volume9
Issue number2
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • antihormone
  • breast cancer
  • resistance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Endocrinology

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