Aromatase immunoreactivity is increased in mammographically dense regions of the breast

Abstract

Mammographic breast density is one of the strongest risk factors for breast cancer. Unfortunately, the biologic basis underlying this association is unknown. This study compared aromatase expression or immunoreactivity (IR) in core biopsies from mammographically dense versus non-dense regions of the breast to examine whether estrogen synthesis in the breast is associated with mammographic breast density (MBD) and one possible mechanism through which it may influence breast cancer. Eligible participants were 40+ yrs, had a screening mammogram with visible MBD and no prior cancer or current endocrine therapy. Mammograms were used to identify dense and non-dense regions and ultrasound-guided core biopsies were performed to obtain tissue from these regions. Immunostaining for aromatase employed the streptavidin-biotin amplification method and #677 mouse monoclonal antibody. Aromatase IR was scored in terms of extent and intensity of staining for each cell type (stroma, epithelium, adipocytes) on the histologic section. A modified histological (H)-score provided quantitation of aromatase IR in each cell type and overall. Repeated measures analyses evaluated average differences (βH) in H-score in dense versus non-dense tissue within and across cell types. Forty nine women mean age 50 yrs (range: 40 to 82), participated. Aromatase IR was increased in dense (vs. non-dense) tissue in both the stroma (βH =0.58) and epithelium (βH =0.12) (p<0.01). Adipocytes from non-dense tissue, however, had a greater IR compared to those from dense tissue (βH =-0.24, p<0.01). An overall H-score which integrated results from all cell types demonstrated that aromatase IR was twice as great for dense (mean H-score=0.90, SD=0.53) vs. non-dense (mean H-score=0.45, SD=0.39) breast tissue (βH =0.45; p<0.001). Overall, aromatase IR was greater for mammographically dense vs. non-dense tissue and may partly explain how MBD influences breast cancer.

Prostaglandin E2 Inhibits p53 in Human Breast Adipose Stromal Cells: A Novel Mechanism for the Regulation of Aromatase in Obesity and Breast Cancer

“…Comparatively, aromatase transcript expression under conditions examined was negligible compared with ASCs, and we believe that much of the residual expression may come from cells that have not properly differentiated in culture. These findings are also consistent with immunohistochemistry results, demonstrating that aromatase staining is highest in ASCs of the breast (47).…”

Breast Density and Breast Cancer Risk: Understanding of Biology and Risk

“…Vachon et al reported higher aromatase expression in mammographically dense versus nondense regions of 49 healthy volunteers undergoing ultrasound-guided core needle biopsies, supporting the hypothesis that local estrogen production in the breasts influences breast density [4]. This interesting finding, which may also potentially be explained by high breast density causing higher aromatase expression due to, for example, 'mechanical' properties (e.g., cell density) of dense breast tissue [45], has not been replicated to date.…”

“…Numerous studies have investigated the relationship (measured within or between study subjects) between mammographic density and the amount or proportion of epithelial cells, adipose tissue, and/or stroma in breast tissue samples [4,20,[23][24][25][26][27][28][29]. Consistently, these studies report a positive association between mammographic density and the amount or proportion of stroma and/or collagen.…”

“…Consistently, these studies report a positive association between mammographic density and the amount or proportion of stroma and/or collagen. Likewise, the amount or proportion of adipose tissue has been consistently inversely associated with mammographic density [4,20,25,28,29]. The studies examining the association between mammographic density and the amount or proportion of epithelial cells (in some studies measured as ducts or lobules or glandular area rather than epithelial cells [24,26,28], or total nuclear area rather than epithelial nuclear area [23]) are somewhat mixed, although all studies report a positive association [4,20,[23][24][25]27] or no association [26,28,29].…”

Is Mammographic Density a Biomarker to Study the Molecular Causes of Breast Cancer?

“…A recent study assessed the association between breast tissue aromatase expression, a ratelimiting enzyme in the estrogen pathway, and mammographic density (Vachon et al, 2011). They looked for this association among 49 healthy Caucasian women aged from 40-82 years old.…”