Antiestrogens: structure-activity relationships and use in breast cancer treatment

    1. S Mader1,2
    1. 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada
    2. 2Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada
    3. 3Department of Chemistry, McGill University, Montréal, Québec, Canada
    1. Correspondence should be addressed to S Mader; Email: sylvie.mader{at}


    About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action. AEs are typically classified as selective estrogen receptor modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation. Characterization of second- and third-generation AEs, however, suggests the induction of diverse ERα structural conformations, resulting in variable degrees of receptor downregulation and different patterns of systemic properties in animal models and in the clinic.

    • Received 28 September 2016
    • Accepted 11 October 2016
    • Made available online as an Accepted Preprint 11 October 2016

    GraphicThis work is licensed under a Creative Commons Attribution 3.0 Unported License.

    | Table of Contents