Aromatase expression in atypical ductal hyperplasia in women.
OBJECTIVE
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.
University of Virginia Health Sciences System, Charlottesville, VA, USA. RJS5y@virginia.edu.
R J
RJ
Santen
Mayo Clinic, Jacksonville, FL, USA.
D C
DC
Radisky
Mayo Clinic, Rochester, MN, USA.
A
A
Degnim
Mayo Clinic, Rochester, MN, USA.
M H
MH
Frost
Mayo Clinic, Rochester, MN, USA.
C M
CM
Vachon
Mayo Clinic, Rochester, MN, USA.
K
K
Ghosh
Tohoku University School of Medicine, Sendai, Japan.
F
F
Guestini
Tohoku University School of Medicine, Sendai, Japan.
K M
KM
McNamara
Tohoku University School of Medicine, Sendai, Japan.
H
H
Sasano
D000328:Adult; D001141:Aromatase / Q000235:genetics*; D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000235:genetics
D011960:Receptors, Estrogen; D001141:Aromatase
Aromatase; Atypical ductal hyperplasia; Breast cancer; Risk factors