Table 2.

Preclinical studies on breast tissue.

	Model	Results
Song et al. [23]	MCF-7 breast cancer cells	(i) BZA blocked CE-induced stimulation, including DNA synthesis, reduction of apoptosis, expression of cMyc, pS2, and WNT1-inducible signaling pathway protein 2
Wardell et al. [24]	MCF-7 breast cancer cells	(i) BZA showed inverse agonist activity on many genes regulated by estradiol
Chang et al. [25]	MCF-7 breast cancer cells and microarrays	(i) BZA, RLZ, and LAS inhibited the proliferation of breast cancer cells induced by CE, with the following antagonist power: BZA > RLX > LAS (ii) BZA inhibited a group of genes regulated by CE; this profile is different from those of RLX and LAS
Peano et al. [26]	Ovariectomized mice	(i) The stimulating effects of CE on the expression of amphiregulin (a marker of ductal proliferation) were antagonized by BZA > RLX > LAS (ii) BZA was more effective than RLX and LAS in reducing ductal growth
Song et al. [23]	Ovariectomized mice	(i) BZA blocked gene expression induced by CE and the growth of mammary terminal ducts and acini (ii) BZA blocked tumor growth and gene expression in mice with MCF-7 xenografts
Ethun et al. [27]	Ovariectomized cynomolgus macaques	(i) 6-month treatment with BZA/CE significantly reduced the increase in epithelial density, the growth, and the ductal proliferation induced by CE (all p < 0.05) (ii) BZA/CE treatment reduced ER protein expression and activity markers