Abstract

BackgroundPrevious studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-α (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls.MethodsBetween 1995 and 1997 at two sites (Women's College Hospital in Toronto and Kingston General Hospital), 667 women who were scheduled for diagnostic excisional breast biopsies completed a questionnaire providing personal information and agreed to allow analysis of routinely resected tissue. Histological slides with nonneoplastic epithelium were available for 101 cancer cases and 200 biopsy controls in Toronto and for 105 cancer cases and 119 controls in Kingston. Nonneoplastic epithelium was examined with immunohistochemical assays to determine the percent of epithelial cells staining for ER and PR. Unconditional logistic regression was used to calculate odds ratios (OR) stratified by study site.ResultsThe ER content of nonneoplastic tissue was higher in cases than biopsy controls in unadjusted analyses; after adjustment for age, however, a weak association remained in only one of the study sites. After adjustment for age, the PR content of nonneoplastic tissue was slightly lower in breast cancer cases than controls in one study site. Furthermore, this inverse association was confined to women with PR negative breast cancer in comparison to the controls. No interaction between ER and PR content of nonneoplastic tissue was observed in relation to the odds of having breast cancer.ConclusionThe results of this study are consistent with only a slight indication of increased ER levels in nonneoplastic tissue in breast cancer cases relative to controls. This study contributes to the understanding of breast cancer by examining both ER and PR in nonneoplastic tissue. Limitations remain, however, such as the necessity of using as controls women with benign breast changes, difficulties in selecting the appropriate tissue for analysis, and tissue sampling concurrent to diagnosis.

Highlights

  • Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk

  • Because breast epithelial cell proliferation is related to both estrogen and progesterone, and progesterone acts through its own receptor [3], levels of the progesterone receptor (PR) may be important in breast carcinogenesis

  • When the 206 cases and 319 controls, the subset of subjects with measurements for estrogen receptor-α (ER) and PR in nonneoplastic tissue, were compared with the total group of 267 cases and 400 controls who had completed a questionnaire, it was found that more subjects from Toronto (27.1%) had missing receptor results than from Kingston (11.8%); this was observed for both cases and controls

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Summary

Introduction

Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-α (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls. In conjunction with progesterone, are mitogenic to breast epithelial cells. Because breast epithelial cell proliferation is related to both estrogen and progesterone, and progesterone acts through its own receptor [3], levels of the progesterone receptor (PR) may be important in breast carcinogenesis. In previous case-control studies, Khan and colleagues observed that the proportion of breast epithelial cells expressing ER was higher in women with breast cancer than benign breast disease controls [4,5]

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