Aromatase expression in atypical ductal hyperplasia in women

R. J. Santen, Derek C Radisky, Amy C Degnim, M. H. Frost, Celine M Vachon, Karthik Ghosh, F. Guestini, K. M. McNamara, H. Sasano

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: To determine the levels of aromatase in atypical ductal hyperplasia (ADH) lesions, tissue surrounding the ADH, and in dense and non-dense normal breast tissue. We postulated that excess aromatase in breast tissue might, through production of increased estrogen, drive the carcinogenic process. Estrogens and their metabolites are thought to contribute to the development of breast cancer through estrogen receptor-mediated mechanisms and genotoxic effects of estrogen metabolites. ADH is a benign lesion of the breast which is associated with substantially increased risk for subsequent development of breast cancer. After 25 years, approximately 30% of women with ADH develop breast cancer. In women with three or more separate ADH lesions at the same time, 47% will develop breast cancer over that time period. Another important risk factor for breast cancer is the presence of mammographically dense breast tissue. Methods: We utilized quantitative immunochemical analysis of aromatase in biopsy tissue to test this possibility. Previously published results comparing dense with non-dense breast tissue in normal women (Vachon et al. Breast Cancer Res Treat 125:243–252, 2011) were used for comparisons with ADH. A well-characterized histochemical H-score was employed for quantitative assessment of aromatase in the various tissue studied. Results: The H-score of aromatase staining was statistically significantly higher (p = 0.003) in the ADH epithelium than surrounding epithelial tissue. In order of H-score from highest to lowest were ADH, issue surrounding ADH, dense normal and non-dense normal breast tissues. The levels of aromatase in a subset of women with ADH who went on to develop breast cancer were not higher than in women who did not. Conclusions: We suggest from these studies that overexpression of aromatase in breast tissue and its resultant increase in estradiol levels may contribute to the later development of breast cancer in women with ADH.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Mar 23 2017

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Aromatase
Breast
Breast Neoplasms
Estrogens
Epithelium
Estrogen Receptors
Estradiol
Staining and Labeling

Keywords

  • Aromatase
  • Atypical ductal hyperplasia
  • Breast cancer
  • Risk factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Aromatase expression in atypical ductal hyperplasia in women. / Santen, R. J.; Radisky, Derek C; Degnim, Amy C; Frost, M. H.; Vachon, Celine M; Ghosh, Karthik; Guestini, F.; McNamara, K. M.; Sasano, H.

In: Breast Cancer Research and Treatment, 23.03.2017, p. 1-7.

Research output: Contribution to journalArticle

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abstract = "Purpose: To determine the levels of aromatase in atypical ductal hyperplasia (ADH) lesions, tissue surrounding the ADH, and in dense and non-dense normal breast tissue. We postulated that excess aromatase in breast tissue might, through production of increased estrogen, drive the carcinogenic process. Estrogens and their metabolites are thought to contribute to the development of breast cancer through estrogen receptor-mediated mechanisms and genotoxic effects of estrogen metabolites. ADH is a benign lesion of the breast which is associated with substantially increased risk for subsequent development of breast cancer. After 25 years, approximately 30{\%} of women with ADH develop breast cancer. In women with three or more separate ADH lesions at the same time, 47{\%} will develop breast cancer over that time period. Another important risk factor for breast cancer is the presence of mammographically dense breast tissue. Methods: We utilized quantitative immunochemical analysis of aromatase in biopsy tissue to test this possibility. Previously published results comparing dense with non-dense breast tissue in normal women (Vachon et al. Breast Cancer Res Treat 125:243–252, 2011) were used for comparisons with ADH. A well-characterized histochemical H-score was employed for quantitative assessment of aromatase in the various tissue studied. Results: The H-score of aromatase staining was statistically significantly higher (p = 0.003) in the ADH epithelium than surrounding epithelial tissue. In order of H-score from highest to lowest were ADH, issue surrounding ADH, dense normal and non-dense normal breast tissues. The levels of aromatase in a subset of women with ADH who went on to develop breast cancer were not higher than in women who did not. Conclusions: We suggest from these studies that overexpression of aromatase in breast tissue and its resultant increase in estradiol levels may contribute to the later development of breast cancer in women with ADH.",
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AU - Degnim, Amy C

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AU - Ghosh, Karthik

AU - Guestini, F.

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AU - Sasano, H.

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