Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

Abstract

Context Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11β-hydroxysteroid dehydrogenase (HSD) 1, and 17β-HSDs. The contribution of steroid hormones produced by adjacent adipose tissue for the progression and survival of breast tumors is unknown. Objective To quantify estrogens (estradiol, estrone) and glucocorticoids (cortisol, cortisone) in breast adipose tissue from both healthy and diseased women and their relationships with adiposity indices and breast cancer prognostic markers. Design and setting Breast adipose tissue was collected at time of surgery. Patients Pre- and postmenopausal women undergoing partial mastectomy for treatment of breast cancer (n = 17) or reduction mammoplasty (n = 6) were studied. Interventions Relative estrogen and glucocorticoid amounts were determined by liquid chromatography tandem mass spectrometry. Results The targeted steroids were reliably detected and quantified in mammary adipose tissues. Women with ER+/PR+ tumor had higher relative estradiol amount than women with ER–/PR– tumor (P < .05). The ratio of estradiol-to-estrone was higher in lean women than in women with a body mass index (BMI) ≥ 25 kg/m2 (P < .05). Mixed-model analyses showed that estradiol, cortisone, and cortisol were negatively associated with tumor size (P < .05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < .05) independently of BMI. Conclusions We reliably quantified estrogens and glucocorticoids in breast adipose tissue from healthy women and women suffering from breast cancer. Our findings suggest that smaller breast tumors are associated with higher relative amounts of estradiol and cortisol in adipose tissue.

The Importance of Breast Adipose Tissue in Breast Cancer

“…Estrogen secreted in such a fashion in the breast increases the concentration of estrogen in the breast by 10 times in comparison with the concentration present in the circulation, thereby increasing the risk of BC [201]. Among BC patients, our group found higher levels of estradiol in breast adipose tissue of women diagnosed with ER-positive BC as compared to those with ER-negative BC [202].…”

Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction

“…Our data showed increased aromatase activity, mirrored by the estrogen-to-androgen ratio, and the specific increase of aromatase CYP19A1 in VAT of women with visceral obesity and adipose tissue dysfunction. Aromatase is known to be significantly affected by total adipose tissue mass (68,69), probably due to the fact that its expression is increased with adipocyte differentiation (65). Indeed, both BMI and WC being indices of general and visceral adiposity, correlate positively with CYP19A1 expression in pre-menopausal (70) but not post-menopausal women (19).…”

Increased Adipose Tissue Indices of Androgen Catabolism and Aromatization in Women With Metabolic Dysfunction

“…Our data showed increased aromatase activity, mirrored by the estrogen-to-androgen ratio, and the specific increase of aromatase CYP19A1 in VAT of women with visceral obesity and adipose tissue dysfunction. Aromatase is known to be significantly affected by total adipose tissue mass ( 69 , 70 ), probably due to the fact that its expression is increased with adipocyte differentiation ( 66 ). Indeed, both BMI and WC, being indices of general and visceral adiposity, correlate positively with CYP19A1 expression in premenopausal ( 71 ) but not postmenopausal women ( 19 ).…”