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Table 1 Preclinical results

From: Breast-related effects of selective estrogen receptor modulators and tissue-selective estrogen complexes

Study reference Study design/model Key results
In vitro studies   
Berrodin et al. [97] (2009) Multiplex ERα-cofactor peptide interaction assay LAS and RLX completely inhibited CE-mediated recruitment of all cofactor peptides to the ERα-ligand-binding domain, whereas CE/BZA inhibited the CE-mediated recruitment of some, but not all, peptides.
GeneChip microarray
CE/BZA gene expression profile was significantly different from CE/LAS or CE/RLX.
CE/RLX, CE/LAS, and CE/BZA antagonized genes involved in cell cycle regulation and growth hormone signaling; CE/RLX and CE/LAS also antagonized expression of a set of CE-regulated genes not affected by CE/BZA.
Chang et al. [62] (2010) MCF-7 cell proliferation assays CE/RLX, CE/LAS, and CE/BZA all antagonized CE-stimulated proliferation, with antagonism levels in the following order: BZA > RLX > LAS.
GeneChip microarray
CE/BZA gene expression profile was significantly different from CE/LAS or CE/RLX.
In vivo studies   
Crabtree et al. [64] (2008) Ovariectomized female mice BZA and RLX (not LAS) reduced estradiol-induced mammary gland end bud proliferation.
Estrogen-responsive marker studies in the mammary gland showed that BZA, RLX, and LAS all function as ER antagonists but have different degrees of agonist activity.
Peano et al. [98] (2009) Ovariectomized mice BZA completely inhibited CE-induced increases in ductal tree branch points; RLX and LAS only partially inhibited CE-induced effects.
Song et al. [30] (2012) Ovariectomized mice with human MCF-7 breast cancer xenografts BZA blocked the estrogenic effects of CE and estradiol (including ductal length, terminal end bud development, proliferation, apoptosis, and gene expression changes).
BZA inhibited estradiol-induced tumor growth and weight.
Ethun et al. [99] (2012) Ovariectomized cynomolgus monkeys CE/BZA antagonized CE-stimulatory effects on total breast epithelial density, Ki67 staining, markers of ERα activity, and lobular size.
BZA alone had neutral effects on all outcomes.
  1. BZA, bazedoxifene; CE, conjugated estrogens; ER, estrogen receptor; LAS, lasofoxifene; RLX, raloxifene.
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