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



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.



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.



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.



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.



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.
Metabolism and Cancer Laboratory, Centre for Cancer Research, Hudson Institute of Medical Research, and Monash University, Clayton, Victoria 3168, Australia.
Kristy A
KA
Brown
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065.|Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Neil M
NM
Iyengar
Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York 10065.
Xi Kathy
XK
Zhou
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065.|Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Ayca
A
Gucalp
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Kotha
K
Subbaramaiah
Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York 10065.
Hanhan
H
Wang
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Dilip D
DD
Giri
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Monica
M
Morrow
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10065.
Domenick J
DJ
Falcone
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Nils K
NK
Wendel
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Lisle A
LA
Winston
Departments of Medicine and Oncology, McGill University, Montreal, Quebec, Canada H3T 1E2.
Michael
M
Pollak
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Anneloor
A
Dierickx
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065.|Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Clifford A
CA
Hudis
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Andrew J
AJ
Dannenberg
D052242:Adiponectin / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000276:immunology*; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms; D002097:C-Reactive Protein / Q000276:immunology*; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000276:immunology*; D020738:Leptin / Q000378:metabolism*; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause; D017697:Premenopause; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D001141:Aromatase