Expression of estrogen receptors (alpha, beta) and insulin-like growth factor-I in breast tissue from surgically postmenopausal cynomolgus macaques after long-term treatment with HRT and tamoxifen.
The novel estrogen receptor ERbeta could be a key factor for proliferation and breast cancer risk. In a primate model for long-term HRT, surgically postmenopausal cynomolgus macaques were treated for 35 months with conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE+MPA and tamoxifen (n=5 in all groups). The immunohistochemical expression of ERalpha, ERbeta and IGF-I in breast tissue was quantified by image analysis. Overall the levels of ERbeta were higher than for ERalpha. In untreated animals, the median area of positive cells was 58% and 21%. The lowest levels for ERbeta were seen during treatment with CEE/MPA (3%) and in this group the expression of ERbeta was lower than for ERalpha. Tamoxifen had effects similar to estrogen. ERbeta may have a role to modulate the proliferative response following activation of ERalpha. The results suggest that hormonal treatments have a different influence on the balance ERbeta/ERalpha in breast tissue.