Histologic changes in the breast with menopausal hormone therapy use

Abstract

Objective-This retrospective study systematically compared mammographic density with histology in women receiving or not receiving menopausal hormone therapy (HT).Design-This study was approved by the institutional review board. Twenty-eight postmenopausal women using HT were matched with 28 postmenopausal women not using HT at the time of breast cancer diagnosis. Noncancerous tissue from mastectomy specimens was examined histologically to quantitate the content of fibrous stroma, ducts, and lobule types 1, 2, and 3. Tissue samples were also evaluated for estrogen receptor, progesterone receptor, and Ki67 activity in the ducts and lobules. Breast density was quantified by digitizing the contralateral mammogram and computer-assisted interactive thresholding.Results-High breast density in women using HT was correlated with greater fibrous stroma (P = 0.020) and lobule type 1 (P = 0.016). Breast density also correlated with Ki67 activity in the ducts (P = 0.031) and lobules (P = 0.023) for both groups combined. Estrogen and progesterone receptors did not correlate with either breast density or HT use.Conclusions-Increased fibrous stroma and lobule type 1 are associated with increasing mammographic density in women using HT, independent of estrogen and progesterone receptor up-regulation. These findings suggest that increased breast density may be mediated through a paracrine effect. The increase in breast cancer risk with HT use may be due to an increase in target lobule type 1 cells.

Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues

“…This result is in line with most of the previous studies [7,8,10,15,25]. Only one study, including benign breast tissue from 56 postmenopausal women found that high mammographic density was associated with increased levels of epithelial Ki-67 [11]. The assessment of cell proliferation can be challenging, as it is influenced by many factors, such as age and menstrual cycle.…”

“…Similar to other studies [7,8,11,15], we found no association between mammographic density and expression of epithelial hormone receptors ER and PR in any of our statistical models. Epidemiological studies have shown that mammographic density is not associated with any particular breast cancer sub-type [26,27], while some studies suggest that mammographic density is more strongly associated with ER-positive rather than ER-negative breast cancers [28,29].…”

“…The positive associations of mammographic density with stromal and epithelial tissues have resulted in investigations of cell proliferation markers such as Ki-67, with inconsistent results [7,8,11,12]. Numerous factors that are associated with breast cancer reflect hormonal exposure thus suggesting a hormonally linked reduction in susceptibility to carcinogenesis [13,14].…”

“…Numerous factors that are associated with breast cancer reflect hormonal exposure thus suggesting a hormonally linked reduction in susceptibility to carcinogenesis [13,14]. The few studies that have investigated the relation between mammographic density and epithelial hormone receptors for oestrogen receptor (ER) and progesterone receptor (PR) in breast tissues have thus far not found any significant correlations [7,8,11,15].…”

Diffusion tensor imaging in the normal breast: influences of fibroglandular tissue composition and background parenchymal enhancement

“…As a result, it would be expected that DTI values would be the same across different FGT compositions because even in a predominantly fatty breast we are creating ROI's in the visually most fibroglandular region which stands to reason that it should be no different than a sample of a fibroglandular region in an overall extremely glandular breast. Our findings are additionally supported by histologic examinations that show that the number of ducts in a breast is constant and independent of overall mammographic density and that mammographic density is more a reflection of the amount of fibrous stroma [19]. …”