Estrogens and glucocorticoids in mammary adipose tissue: Relationships with body mass index and breast cancer features

CONTEXT: Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11β-HSD1 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 post-menopausal women undergoing partial mastectomy for treatment of breast cancer (n=17) or reduction mammoplasty (n=6) were studied. INTERVENTIONS: Estrogen and glucocorticoid relative 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 estradiol levels than women with ER-/PR- tumor (P < 0.05). Ratio of estradiol-to-estrone was higher in lean women compared to women with a BMI ≥ 25 kg/m2 (P < 0.05). Mixed-model analyses showed that estradiol, cortisone and cortisol were negatively associated with tumor size (P < 0.05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < 0.05) 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 levels of estradiol and cortisol in adipose tissue.