Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.

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.

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.

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.

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.

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.

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.

• Authors: Kristy A Brown, Neil M Iyengar, Xi Kathy Zhou, Ayca Gucalp, Kotha Subbaramaiah, Hanhan Wang, Dilip D Giri, Monica Morrow, Domenick J Falcone, Nils K Wendel, Lisle A Winston, Michael Pollak, Anneloor Dierickx, Clifford A Hudis, Andrew J Dannenberg
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 5 Pg. 1692-1701 (05 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28323914 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• ADIPOQ protein, human
• Adiponectin
• Blood Glucose
• Cholesterol, HDL
• Cholesterol, LDL
• IL6 protein, human
• Insulin
• Interleukin-6
• Leptin
• RNA, Messenger
• Triglycerides
• C-Reactive Protein
• Cholesterol
• Aromatase

Topics

• Adiponectin (metabolism)
• Adipose Tissue, White (immunology)
• Adult
• Aged
• Aromatase (genetics, metabolism)
• Blood Glucose (metabolism)
• Body Mass Index
• Breast (metabolism)
• Breast Neoplasms
• C-Reactive Protein (immunology)
• Cholesterol (metabolism)
• Cholesterol, HDL (metabolism)
• Cholesterol, LDL (metabolism)
• Female
• Gene Expression Regulation, Developmental
• Humans
• Inflammation
• Insulin (metabolism)
• Insulin Resistance
• Interleukin-6 (immunology)
• Leptin (metabolism)
• Menopause (metabolism)
• Middle Aged
• Multivariate Analysis
• Postmenopause
• Premenopause
• RNA, Messenger (metabolism)
• Triglycerides (metabolism)