Endocrine Abstracts (2019) 65 P231 | DOI: 10.1530/endoabs.65.P231

Mammary adipose tissue steroid activation and its relevance for breast cancer prognosis

Sofia Laforest1,2,3, Nina Denver4,5,6, Natalie ZM Homer5, Francine Durocher1, Brian R Walker3,7, Ruth Andrew3,5 & Andre Tchernof1,2

1CRCHU-UL, Quebec, Canada; 2IUCPQ, Quebec, Canada; 3BHF/CVS, QMRI, U of Edinburgh, Edinburgh, UK; 4ICAMS, U of Glasgow, Glasgow, UK; 5MS Core, Edinburgh CRF, Edinburgh, UK; 6SIPBS, U of Strathclyde, Glasgow, UK; 7IGM, Newcastle University, Newcastle, UK

Background: Adipose tissue dysfunction could partially explain the well-demonstrated association between obesity and survival in breast cancer (BC). Oestrogen and glucocorticoid concentrations and their respective activation enzymes, oestrogenic 17β-hydroxysteroid dehydrogenases (17βHSDs) and aromatase, and 11βHSD1 are increased in adipocyte hyperplasia and hypertrophy, supporting the hypothesis of a potential role for locally generated steroids in obesity-associated BC. The purpose of this study was to assess the relationships between oestrogens (oestradiol, oestrone) and the inert substrate and active product of 11βHSD1 (cortisone and cortisol, respectively) in breast adipose tissue with adiposity and BC prognostic factors.

Methods: Mammary adipose tissue was collected with ethical approval in pre- and postmenopausal women undergoing partial mastectomy for treatment of BC (n=17) or reduction mammoplasty (n=6). A validated liquid chromatography-tandem mass spectrometry method was developed to determine oestrogen and glucocorticoid amounts in adipose tissue. Hormone levels differences were assessed using Student’s test. Mixed-models were computed to test the association between prognostic factors and hormonal levels.

Results: Oestrogens and glucocorticoids were reliably quantified in mammary adipose tissues (200 mg). Oestradiol, cortisone and cortisol were negatively associated with tumour size (P<0.05). The cortisol-to-cortisone ratio was negatively associated with tumour stage (P<0.05) independently of BMI, suggesting a decreased activity of 11βHSD1. Women with hormone receptor-positive tumour had higher oestradiol and oestrone levels than women with hormone receptor-negative tumour (P<0.05). Ratio of oestradiol-to-oestrone was higher in lean women compared to women with a BMI≥25 kg/m2 (P<0.05), suggesting little impact of 17βHSDs conversion per mass unit in adipose tissue in obese BC.

Conclusions: Oestrogens and glucocorticoids were detected in breast adipose tissue healthy women as well as those suffering from BC. Oestrogens levels, but not glucocorticoids levels, were negatively associated with adiposity. Our findings suggest that smaller breast tumours are associated with higher levels of oestradiol, cortisone and cortisol in adipose tissue.

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