Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk

Abstract

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR) 5 0.39; p 5 0.015) and progesterone (OR 5 0.40; p 5 0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well-known association of expression of these receptors in the malignant tissue and better breast cancer prognosis. ' 2008 Wiley-Liss, Inc.Key words: breast cancer; estrogen; progesterone; receptors There is a consensus that estrogens play a central role in the etiology of breast cancer, and results from both observational studies and randomized trials have also implicated progestins. 1-3 The effects of estrogens and progesterone in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. 4,5 Khan et al. have suggested that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. 6 They undertook a study to evaluate this hypothesis by examining expression of estrogen receptors (at that time only estrogen receptors alpha were routinely evaluated) in the apparently normal mammary gland tissue adjacent to the pathological tissue in 174 women with breast cancer and 202 women with benign breast diseases (BBDs). 7 The results were interpreted as indicating that overexpression of estrogen receptors alpha in normal breast epithelium may augment estrogen sensitivity and, hence, the risk of breast cancer. In an editorial accompanying this study, the authors found the results intriguing, but also pointed out some limitations of the study and the need for additional investigations. 8 Since then, the results of 2 partially overlapping ecological studies in Asia 9,10 were interpreted as compatible with...

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“…The expression of ER α and PR in normal mammary tissue adjacent to the pathological tissue compared to women with benign breast disease shows that the overexpression of ER α and PR is associated with reduced breast cancer risk, but increased age at the diagnosis of hormone receptor-positive tumors is associated with higher disease-specific mortality (Lagiou et al 2009; van de Water et al 2012). In HER2-positive tumors, ER α and PR are associated with AR co-expression and lower proliferative activity, while AR-negative/ER α -negative tumors were associated with highest proliferative activity and histological grade (Lin Fde et al 2012).…”

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