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

Laforest, S. et al. (2019) Estrogens and glucocorticoids in mammary adipose tissue: Relationships with body mass index and breast cancer features. Journal of Clinical Endocrinology and Metabolism, 105(4), e1504-e1516. (doi: 10.1210/clinem/dgz268) (PMID:31853538) (PMCID:PMC7065843)

Abstract

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. 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. Breast adipose tissue was collected at time of surgery. Pre- and post-menopausal women undergoing partial mastectomy for treatment of breast cancer (n=17) or reduction mammoplasty (n=6) were studied. Estrogen and glucocorticoid relative amounts were determined by liquid chromatography-tandem mass spectrometry. 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. 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.

• Item Type: Articles
• Additional Information: This work was supported by an inter-center grant from the CMDO to AT, CD and FD. SL is the recipient of PhD scholarships from Fonds de recherche du Québec-santé (FRQS) and the Canadian Institutes of Health Research (CIHR). SL’s internship in RA’s lab was made possible thanks to the support of the Institute of Nutrition and Functional Foods and the scholarship from the International internship program of the Fonds de recherche Nature et Technologies du Québec (FRQNT) as well as a Michael Smith Foreign Study Supplement travel scholarship. CD holds an Investigator Awards (Senior) from the FRQS. RA is funded by the Wellcome Trust. BRW is a Wellcome Trust Senior Investigator.
• Keywords: adiposity, breast cancer, cortisol, cortisone, estradiol, estrone.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Denver, Nina
• Authors: Laforest, S., Pelletier, M., Denver, N., Poirier, B., Nguyen, S., Walker, B. R., Durocher, F., Homer, N. Z.M., Diorio, C., Andrew, R., and Tchernof, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Clinical Endocrinology and Metabolism
• Publisher: Oxford University Press
• ISSN: 0021-972X
• ISSN (Online): 1945-7197
• Published Online: 20 December 2019
• Copyright Holders: Copyright © 2019 Endocrine Society
• First Published: First published in Journal of Clinical Endocrinology and Metabolism 105(4):e1504-e1516
• Publisher Policy: Reproduced under a Creative Commons license