Early life exposure to flaxseed reduces mammary ER-β expression and increases susceptibility to mammary tumorigenesis in rats.

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Flaxseed contains breast cancer risk -reducing bioactive food components, such as lignans, but also heavy metal cadmium that acts as an endocrine disruptor. Our previous studies have shown that feeding pregnant or lactating rats whole or defatted flaxseed diet increases their female offspring’s susceptibility to develop mammary tumors. We now investigated whether the increase in breast cancer risk in these rats was associated with changes in the expression of estrogen receptors (ER) α and ER-β, or cell proliferation, when assessed in the normal mammary glands of 8-week-old rats. For that purpose, pregnant or lactating rats were fed diets containing 0%, 5% or 10% flaxseed. In utero 10% flaxseed exposure increased lobular ER-α protein levels (p<0.05) and reduced lobular ER-β levels (p<0.03) (assessed using immunohistochemistry), but had no effects on cell proliferation in either TEBs, lobules or ducts. Lactational exposure to flaxseed had no effects of mammary ER-α levels or cell proliferation, but 10% flaxseed reduced ER-β levels in the TEBs (p<0.05) and lobules (p<0.001). These findings suggest that down-regulation of ER-β in the mature mammary gland is a common feature to both fetal and prepubertal flaxseed exposures and might be associated with the increase in mammary cancer risk seen in the offspring of dams fed 10% flaxseed diet either during pregnancy or lactation.