Abstract
BackgroundPostmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients.MethodsFormalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS.ResultsCLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72).ConclusionsCLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.
Highlights
Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk
crown-like structures (CLS) were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones
We examined whether tertiles of hormone levels were associated with the presence of CLS using logistic regression, with CLS as the outcome variable and tertiles of each hormone examined as explanatory variables
Summary
Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Within breast adipose tissue, the ratio of testosterone to estradiol was statistically significantly lower than in serum, suggesting that hormone metabolism or other tissue factors might affect hormone concentrations locally in the breast, and could affect the behavior of immediately adjacent epithelium. These findings support the hypothesis that aromatization of androgens to estrogens in breast fat might increase estrogen levels, and potentially exert local influences on carcinogenesis [8, 9]. We hypothesize that crown-like structures (CLS) may represent tissue factors that influence local hormone aromatization
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