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

Abstract

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...

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions

“…6,9,10 Entry biopsies were performed between 1965 and 1982. The authors reviewed the available histologic slides from 54 women (70%), and for the remaining 23 women, information was obtained from pathology reports (n ¼ 13), subject interviews or medical records (n ¼ 8), and death certificates (n ¼ 2).…”

Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERα-positive breast carcinomas

“…In a nested case–control study, it has recently been demonstrated that patients with increased numbers of epithelial cells expressing estrogen receptor alpha (ERα) in normal lobular units are at increased risk of subsequent invasive breast cancer [11]. These results suggest that overexpression of estrogen receptor in benign breast epithelium may increase estrogen sensitivity, thereby creating a permissive state that can lead to malignancy.…”

Prognostic Significance of Estrogen Receptor Beta in Epithelial Hyperplasia of Usual Type With Known Outcome

“…24 Recently, Gobbi et al designed a similar case-control study of HUT lesions in. 9 The authors analyzed their expression of ER-a manually in HUT foci from cases and control subjects and showed a higher risk of subsequently developing breast cancer in HUT patients with ER-a+ normal lobules (cutoff 10% for positivity). The authors, however, presented their data in the form of positive or negative expression and did not provide median values for the percentages of ER-a expression.…”