Estrogen Receptor Expression in Benign Breast Epithelium and Breast Cancer Risk

Khan, Seema A.; Rogers, Mary A.M.; Khurana, Kamal K.; Meguid, Michael M.; Numann, Patricia J.

doi:10.1093/jnci/90.1.37

Cited by 267 publications

(248 citation statements)

References 14 publications

Supporting

Mentioning

211

Contrasting

Unclassified

Order By: Relevance

“…The hypothesis is also supported by the results of several independent investigations that have shown an increase in the level of estrogen receptor ␣ expression as mammary histology progresses from normal to proliferative to carcinoma in situ and eventually invasive carcinoma 6,7 and by a report from a case-control study that the likelihood of breast cancer increases when there is overexpression of estrogen receptors in the normal epithelium. 8,9 Lastly, a role for normal breast tissue estrogen receptor ␣ expression in carcinogenesis is supported by the findings of an earlier investigation 10 showing significantly higher expression of estrogen receptor ␣ in the normal mammary tissue of Caucasian Australian women than in Japanese women in Japan. It may also be of importance that differences in estrogen receptor ␣ expression, in both the study by Lawson and colleagues 10 and the present study, are much more evident among postmenopausal than premenopausal women, in parallel with the higher international variability of breast cancer incidence in the former than in the latter group.…”

Section: Discussionmentioning

confidence: 72%

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Lawson

Field

Tran

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

We have undertaken a study to examine whether the difference in breast cancer incidence between 2 populations of similar genetic background is reflected in a similar pattern of estrogen receptor ␣ expression in normal mammary gland. Study participants were 92 Japanese women from Sapporo, Japan (mean age 48.2 years) and 49 Japanese women from Honolulu, Hawaii (mean age 45.4 years), who underwent biopsy indicating normal breast tissue or benign, nonproliferative breast disease in hospitals in Sapporo, Japan and Honolulu, Hawaii. The breast tissue samples were formalin-fixed and paraffin-embedded. The estrogen receptor immunohistochemistry assays were conducted using Dako kits. Japanese women in Hawaii, who have a higher incidence of breast cancer compared with Japanese women in Sapporo, also had, as predicted, higher mean percentage of estrogen receptor ␣-positive normal mammary cells (2-tailed test, p ϳ 0.09). The results of our study are compatible with the hypothesis that estrogen receptor ␣ expression in normal mammary tissue increases breast cancer risk and they also indicate that the expression of these receptors is dependent, at least in part, on nongenetic factors. © 2002 Wiley-Liss, Inc. Key words: breast cancer; estrogen receptors; epidemiology; Japanese Endogenous estrogens are central in the etiology of breast cancer in women. [1][2][3][4] Nevertheless, no aspect of estrogen production, metabolism and physiologic effects can fully explain the higher incidence of the disease among Caucasian women in North America, northern Europe or Oceania in comparison with Japanese and Chinese women in their home countries. 5 Because estrogen receptors are mandatory for estrogen response, it has been hypothesized that expression of these receptors in normal breast tissue could be as important as estrogen levels for the determination of breast cancer risk. 6 -9 In a recent paper, we have reported that expression of estrogen receptor ␣ is much higher among Australian Caucasian women than among Japanese women in Japan, in parallel with the much higher breast cancer incidence among the former compared with the latter. 10 The incidence of breast cancer among Japanese women in Hawaii is at least twice as high as that among Japanese living in Japan, although not quite as high as the incidence of breast cancer among Caucasians. 5 This is a well-established pattern for migrants from low to high breast cancer risk countries and their descendants. 11-13 Indeed, this pattern has been used to argue that a large fraction of the variation of breast cancer incidence in women is of exogenous, rather than genetic, etiology. We undertook a study to examine whether the higher breast cancer incidence of Japanese in Hawaii in comparison with Japanese in Japan is reflected in a similar pattern of estrogen receptor ␣ expression in normal mammary gland. This, if detected, would support the hypothesis that the expression of these receptors in normal breast is a risk factor for breast cancer and would also indicate that the expression of t...

show abstract

Section: Discussionmentioning

confidence: 72%

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Lawson

Field

Tran

et al. 2001

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Hence, this study evaluates future breast cancer risk in women who have unequivocally benign lesions. In contrast, Khan et al 18,19 performed a cross-sectional study in which benign epithelium from cases with concurrent breast cancer was contrasted with that of cancer-free controls. These investigators found higher levels of ER expression in the benign epithelium of cases compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units

Gobbi

Dupont

Parl

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Estrogen is associated with many epidemiologic risk factors for invasive breast cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia lacking atypia (EHLA) may influence breast cancer progression. We conducted a nested case-control study of 268 women with biopsy-confirmed EHLA to determine whether immunohistochemical expression of ER␣ in EHLA affects subsequent breast cancer risk. Study subjects could not have a prior or current history of breast cancer or atypical hyperplasia. Knowledge of molecular markers of breast neoplastic progression may help identify women at high risk for breast cancer. Such markers would facilitate the development of prophylactic therapies for premalignant breast disease. 1 Estrogen has long been associated with stimulating the normal growth of breast epithelial cells and may also be associated with many epidemiologic risk factors for invasive breast cancer. Estrogen acts on cells via the estrogen receptors (ERs) to stimulate their mitogenic activity. 2 Comparison of normal and precancerous breast biopsies has shown that ER expression is relatively low in normal epithelium and higher in atypical ductal hyperplasia and carcinomas in situ. 3,4 The earliest lesion associated with breast cancer is epithelial hyperplasia lacking atypia (EHLA), which has a 1.5-to 2-fold increased risk of development of breast cancer. 5-8 A slight increase in ER-positive cells has been described in these earliest lesions. 3 In our study, we investigated the relationship between ER␣ expression in EHLA and subsequent risk of invasive breast cancer. Material and methodsWe conducted a retrospective nested case-control study of women from the Nashville Breast Cohort Study. 5,9 -11 This cohort consists of women who underwent benign breast biopsy at 1 of 3 hospitals in Nashville, Tennessee. Successful follow-up in this cohort has been achieved for 90% of study subjects. Women with prior or concurrent invasive breast cancer were excluded from this cohort. Cohort members were eligible for inclusion in this study if their entry biopsy contained EHLA and were performed between 1965 and 1982. This study subcohort consisted of 1,680 women. The average length of follow-up for these patients was 15.4 years. Cases consisted of all eligible subjects who subsequently developed invasive breast cancer. Two controls were selected for each case matched by age at biopsy and year of biopsy. To be selected as a control for a specific case, a patient had to be in the risk set for that case at the time when the case patient developed breast cancer, 12 that is, her breast cancer-free follow-up had to be at least as long as that of the case under consideration. Selected controls could subsequently become cases, which in fact happened for 8 women. Each of these subjects was included as a control in one set of matched case-control triplets and as a case in another. There were 92 cases who developed breast cancer on follow-up who were matched to 184 controls. Since 8 of these controls subsequently became cases, this...

show abstract

“…Only 10-20 % of cells are ERα-positive in normal resting human mammary glands [40][41][42]. This percentage increases in proliferative benign disease, which is often associated with atypical low-grade ductal carcinoma in situ (DCIS).…”

Section: E2 Signaling In Breast Carcinogenesismentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

show abstract

Estrogen Receptor Expression in Benign Breast Epithelium and Breast Cancer Risk

Abstract: The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.

Cited by 267 publications

References 14 publications

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Contact Info

Product

Resources

About