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Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2017 May 01; Vol. 102 (5), pp. 1692-1701. - Publication Year :
- 2017
-
Abstract
- Context: Most estrogen-dependent breast cancers occur after menopause, despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown.<br />Objective: To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi), and systemic markers of metabolic dysfunction.<br />Design, Setting, and Participants: Cross-sectional study of 102 premenopausal (age 27 to 56) and 59 postmenopausal (age 45 to 74) women who underwent mastectomy for breast cancer treatment/prevention.<br />Outcome: Breast tissue was assessed for the presence of crown-like structures and the expression and activity of aromatase. Systemic markers examined include interleukin (IL)-6, insulin, glucose, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP), cholesterol, and triglycerides. Multivariable analysis was performed for aromatase messenger RNA (mRNA) in relation to BMI, WATi, and blood markers.<br />Results: Postmenopausal women had higher BMI and more breast WATi than premenopausal women. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostatic model assessment 2 insulin resistance score were higher in the postmenopausal group. BMI was positively correlated with aromatase mRNA in both pre- and postmenopausal women. Aromatase levels were higher in breast tissue of postmenopausal women, with levels being higher in inflamed vs noninflamed, independent of BMI. Adipocyte diameter and levels of leptin, hsCRP, adiponectin, and high-density lipoprotein cholesterol were more strongly correlated with aromatase in postmenopausal than premenopausal women.<br />Conclusions: Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.<br /> (Copyright © 2017 Endocrine Society)
- Subjects :
- Adult
Aged
Aromatase metabolism
Blood Glucose metabolism
Body Mass Index
Breast Neoplasms
Cholesterol metabolism
Cholesterol, HDL metabolism
Cholesterol, LDL metabolism
Female
Gene Expression Regulation, Developmental
Humans
Inflammation
Insulin metabolism
Insulin Resistance
Middle Aged
Multivariate Analysis
Postmenopause
Premenopause
RNA, Messenger metabolism
Triglycerides metabolism
Adiponectin metabolism
Adipose Tissue, White immunology
Aromatase genetics
Breast metabolism
C-Reactive Protein immunology
Interleukin-6 immunology
Leptin metabolism
Menopause metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 102
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 28323914
- Full Text :
- https://doi.org/10.1210/jc.2016-3606