Estrogen receptor α expression in normal human breast epithelium is consistent over time

Abstract

If increased expression of estrogen receptor ␣ (ER) in benign breast epithelium increases susceptibility to breast cancer, such overexpression should be stable over time. There are no published data regarding this important aspect of ER expression in breast epithelium. We examined the temporal consistency of ER expression in the normal breast tissue of 28 women who had 2 separate breast surgical procedures, at least 6 months apart (mean interval, 2.8 years). Paraffin embedded breast tissue blocks containing an adequate sample of normal breast epithelium and no cancer, were sectioned and processed using the 6F11 antibody and standard immunohistochemical techniques. The ER labelling index (ER LI) was calculated by counting a mean of 2,000 epithelial cells. The median ER LI at first sampling was 13.6 and at second sample 15.5, with R 2 ‫؍‬ 0.34 and p ‫؍‬ 0.001. The ER LI was categorized into high and low values, using a threshold of 10. Twenty-four women (85.7%) showed concordance of high and low expression between the 2 samples (p ‫؍‬ 0.002). There were 11 women who were premenopausal at both time points. Among them, much of the variation in ER LI was explained by differences in the menstrual cycle day at the time of sampling and adding the day of cycle to the regression model substantially improved the correlation between first and second labeling indices. These data suggest that ER expression of normal breast tissue is fairly consistent over time and support the notion that overexpression of ER in normal epithelium is a constant feature of the high risk breast. © 2002 Wiley-Liss, Inc. Key words: estrogen receptor ␣; normal breast epitheliumThe increased expression of estrogen receptor ␣ (ER) protein has been observed in the normal breast epithelium of breast cancer cases 1,2 and lower expression has been shown in women belonging to low risk ethnic groups. 3,4 These findings have raised the possibility that estrogen receptor ␣ overexpression is a risk factor for the development of breast cancer. According to the current paradigm of the role of estrogen in breast cancer development, 1 of the effects of prolonged exposure to estrogen is an increase in the mitotic activity of breast epithelium, thereby increasing the mutation rate and allowing genetic defects to accumulate. 5,6 The role of increased ER expression in this paradigm would be to increase the sensitivity of breast epithelium to ambient estrogen. This model requires that increased ER expression be relatively constant over a period of time, because the cumulative effect of increased estrogen exposure occurs over the long term. There have, to date, been no studies examining the temporal constancy of ER expression in normal breast epithelium over a period of years. Existing crosssectional data point to a trend for estrogen receptor expression to increase with age 2,7 and short term longitudinal studies in premenopausal women have shown that ER expression decreases through the menstrual cycle, 8 although this may not be true in high risk women. 2 This article...

The local hormonal environment and related biomarkers in the normal breast

“…We also observed that the breast epithelium of controls on HRT displayed significantly higher ER expression than that of controls not on HRT, an observation subsequently reproduced by Lawson et al (2001), who showed that obesity also contributes to this higher expression. The notion of increased ERa expression in the highrisk breast is supported by the consistency of high expression over time, demonstrated in a study of 28 women undergoing two separate breast biopsies at least 6 months apart (Khan et al 2002). On categorizing the women into high and low expressers based on an ER labeling index (ER LI) value of 10, there was 86% concordance between the first and second samples.…”

Association between low estrogen receptor positive breast cancer and staining performance

“…The degree of ER expression in normal breast epithelium has been shown to be dependent on biologic factors such as menopausal status and body mass index but may also be related to breast cancer risk and affected by timing within the menstrual cycle and the presence of an adjacent breast carcinoma. [19][20][21][22][23] It has been theorized that ER positive tumors may cause a "field effect", resulting in higher ER expression in normal breast epithelium adjacent to a strongly ER positive tumor due to increased ER gene expression in normal terminal ductal lobular units of patients with ER positive breast carcinomas. 24 However, results of studies evaluating protein expression of ER by IHC in normal epithelium are conflicting.…”

Overexpression of Cyclin E and its Low Molecular Weight Isoforms Cooperate with Loss of p53 in Promoting Oncogenic Properties of MCF-7 Breast Cancer Cells

“…Former studies have identified a role for LMW-Es in early stages of tumor development (Shaye et al, 2009). Moreover, it has been shown that there are high ER expression (Khan et al, 1998;Smith et al, 2001;Khan et al, 2002) and lack of downregulation in ER content despite high level of serum E2 in benign breast epithelium of women with breast cancer (Khan et al, 1999;Chung et al, 2012). Besides E2 can also enhance proteolysis and expression of cyclin E (Hou et al, 2012;Niu et al, 2015).…”