title: Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer.
abstract: Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. In humans, obesity causes subclinical inflammation in visceral and subcutaneous adipose tissue, characterized by necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS). Recently, we found increased numbers of CLS, activation of the NF-κB transcription factor, and elevated aromatase levels and activity in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity → inflammation axis is important for the development and progression of breast cancer. Here, our main objective was to determine if the findings in mouse models of obesity translated to women. Breast tissue was obtained from 30 women who underwent breast surgery. CLS of the breast (CLS-B) was found in nearly 50% (14 of 30) of patient samples. The severity of breast inflammation, defined as the CLS-B index, correlated with both body mass index (P < 0.001) and adipocyte size (P = 0.01). Increased NF-κB binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity → inflammation → aromatase axis is present in the breast tissue of most overweight and obese women. The presence of CLS-B may be a biomarker of increased breast cancer risk or poor prognosis.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Dilip
authors.initials: D
authors.lastname: Giri
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Domenick J
authors.initials: DJ
authors.lastname: Falcone
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.forename: Baoheng
authors.initials: B
authors.lastname: Du
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Crawford
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: Kotha
authors.initials: K
authors.lastname: Subbaramaiah
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
mesh_terms: D017667:Adipocytes / Q000201:enzymology / Q000473:pathology; D001141:Aromatase / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D001940:Breast / Q000201:enzymology / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008499:Medical Records; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D050177:Overweight / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D050151:Subcutaneous Fat
chemical_list: D016328:NF-kappa B; D001141:Aromatase