Study reference | Study design/model | Key results |
---|---|---|
In vitro studies | Â | Â |
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 | Â | Â |
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. |