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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.