TY - JOUR
T1 - Menopause is a determinant of breast aromatase expression and its associations with BMI, inflammation, and systemic markers
AU - Brown, Kristy A.
AU - Iyengar, Neil M.
AU - Zhou, Xi Kathy
AU - Gucalp, Ayca
AU - Subbaramaiah, Kotha
AU - Wang, Hanhan
AU - Giri, Dilip D.
AU - Morrow, Monica
AU - Falcone, Domenick J.
AU - Wendel, Nils K.
AU - Winston, Lisle A.
AU - Pollak, Michael
AU - Dierickx, Anneloor
AU - Hudis, Clifford A.
AU - Dannenberg, Andrew J.
N1 - Funding Information:
This work was supported by National Institutes of Health R01CA185293, National Institutes of Health/National Cancer Institute U54 CA210184-01, the Breast Cancer Research Foundation, the Prevent Cancer Foundation, the Botwinick-Wolfensohn Foundation (inmemory ofMr. andMrs. Benjamin Botwinick), the Victorian Government Operational Infrastructure Support Program, Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748), and by Myrna and Bernard Posner. K.A.B. was supported by the Mavis Robertson Fellowship from the National Breast Cancer Foundation (ECF-16-004) and by National Health and Medical Research Council project grant (GNT1061800). L.A.W. was supported by The Dr. Robert C. and Veronica Atkins Foundation. A.D. was supported by the Mobility Fund of Medicine and Health Sciences (Ghent University). N.M.I. is supported by the Conquer Cancer Foundation of the American Society of Clinical Oncology.
Publisher Copyright:
© 2017 Endocrine Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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 ofmenopause on breast aromatase expression in relation to bodymass 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 premenopausalwomen. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostaticmodel assessment 2 insulin resistance score were higher in the postmenopausal group. BMIwas positively correlated with aromatasemRNA in both pre- A nd 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.
AB - 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 ofmenopause on breast aromatase expression in relation to bodymass 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 premenopausalwomen. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostaticmodel assessment 2 insulin resistance score were higher in the postmenopausal group. BMIwas positively correlated with aromatasemRNA in both pre- A nd 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.
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U2 - 10.1210/jc.2016-3606
DO - 10.1210/jc.2016-3606
M3 - Article
C2 - 28323914
AN - SCOPUS:85019053832
VL - 102
SP - 1692
EP - 1701
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -