title: Metabolic Obesity, Adipose Inflammation and Elevated Breast Aromatase in Women with Normal Body Mass Index.
abstract: Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI (<25 kg/m2) undergoing mastectomy for breast cancer risk reduction or treatment. WAT inflammation was defined by the presence of crown-like structures of the breast (CLS-B) which are composed of dead or dying adipocytes surrounded by macrophages. Severity of inflammation was measured as CLS-B/cm2The primary objective was to determine whether breast WAT inflammation is associated with aromatase expression and activity. Secondary objectives included assessment of circulating factors and breast adipocyte size. Breast WAT inflammation was present in 39% of women. Median BMI was 23.0 kg/m2(range, 18.4-24.9 kg/m2) in women with breast WAT inflammation versus 21.8 kg/m2(range, 17.3-24.6 kg/m2) in those without inflammation (P= 0.04). Breast WAT inflammation was associated with elevated aromatase expression and activity, which increased with severity of inflammation (P< 0.05). Breast WAT inflammation correlated with larger adipocytes (P= 0.01) and higher circulating levels of C-reactive protein, leptin, insulin, and triglycerides (P≤ 0.05). A subclinical inflammatory state associated with elevated aromatase in the breast, adipocyte hypertrophy, and systemic metabolic dysfunction occurs in some normal BMI women and may contribute to the pathogenesis of breast cancer.Cancer Prev Res; 10(4); 235-43. ©2017 AACRSee related article by Berger, p. 223-25.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. iyengarn@mskcc.org ajdannen@med.cornell.edu.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Iyengar
authors.affiliation: Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Brown
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ayca
authors.initials: A
authors.lastname: Gucalp
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Kotha
authors.initials: K
authors.lastname: Subbaramaiah
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Dilip D
authors.initials: DD
authors.lastname: Giri
authors.affiliation: Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Faculty of Applied Medical Science, Taibah University, Medina, Saudi Arabia.
authors.forename: Heba
authors.initials: H
authors.lastname: Zahid
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Priya
authors.initials: P
authors.lastname: Bhardwaj
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Nils K
authors.initials: NK
authors.lastname: Wendel
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Domenick J
authors.initials: DJ
authors.lastname: Falcone
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Samantha
authors.initials: S
authors.lastname: Williams
authors.affiliation: Department of Medicine and Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York. iyengarn@mskcc.org ajdannen@med.cornell.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology*; D000328:Adult; D001141:Aromatase / Q000096:biosynthesis*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008875:Middle Aged
chemical_list: D001141:Aromatase; C561410:CYP19A1 protein, human