title: Preclinical breast effects of a tissue selective estrogen complex (TSEC) including conjugated estrogen with bazedoxifene.
abstract: The first tissue-selective estrogen complex (TSEC), consisting of a combination of a conjugated equine estrogen (CEE) and bazedoxifene (BZA), has been approved for treatment of the menopause in the USA and European Union. We have postulated that this TSEC might block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer growth. This manuscript, representing a presentation at a Festschrift honoring Evan Simpson, reviews our published data BZA blocked the in vitro effects of both estradiol and CEE on cell growth and gene expression in MCF-7 cells. BZA completely blocked CEE- or E2-stimulated ductal and terminal end bud growth of immature murine mammary glands and the growth of experimental breast cancers. These findings provide a rationale for future clinical studies to determine whether this TSEC prevents the growth of occult breast cancer in women.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1416, USA. Electronic address: rjs5y@virginia.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Santen
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1416, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1416, USA.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Wang
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1416, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: Bazedoxifene; Breast cancer; Conjugated equine estrogens; Mammary gland; Tissue-selective estrogen complexes