Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0791-4) contains supplementary material, which is available to authorized users.

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

“…N=20 studies have been identified that were conducted in patients with different cancer types (breast, colorectal, esophageal, endometrial, prostate, and ENT) to investigate the crosstalk between patients’ adipose tissue and carcinomas (see Table 1) (8,64–75). …”

“…The majority of human studies have been conducted in breast cancer patients (n=7) (66,68,70,75–78). Other studies have been implemented in cancers of the gastrointestinal tract (colorectal cancer (n=4) (8,64,71,73), esophageal cancer (n=2) (65,79), combined (colorectal and esophageal) (n=1) (80)), reproductive cancer (endometrial (n=1) (72), prostate (n=4) (69,74,81,82)), or ENT tract (tongue (n=1) (83)).…”

“…Of interest, while the risk for breast cancer is increased for obese postmenopausal women, premenopausal obese women have a lower incidence of breast cancer (84). Adipocytes comprise about 90% of the normal breast tissue and thus, the question of adipocytes contributing directly to tumor progression as part of the tumor stroma has been addressed in several studies (66,68,70,75,76). Breast cancer stroma can be classified into adipose stroma cancer (>50% of cells are adipocytes), and fibrous stroma cancer (100% of cells are fibroblasts) or a combination of both stroma types (<100% of cells are fibroblasts, <50% are adipocytes) (76).…”

“…The most recent study collected benign breast tissue of n=83 postmenopausal women who were recently diagnosed with invasive breast cancer (75). Mullooly et al focused on the association between crown-like structures and steroid hormones in breast adipose tissue (75).…”

Crown-like Structures in Breast Adipose Tissue from Normal Weight Women: Important Impact

“…17). Importantly, an increase in the estrone:androstenedione ratio was found in breast tissue from postmenopausal breast cancer patients that contained CLS (18). Interestingly, inflamed adipose tissue has recently been shown to release cell-free DNA capable of stimulating insulin resistance (19).…”