title: Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients.
abstract: Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients.
  
  
  
  Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS.
  
  
  
  CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03-0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04-0.72).
  
  
  
  CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. maeve.mullooly@nih.gov.|Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. maeve.mullooly@nih.gov.
authors.forename: Maeve
authors.initials: M
authors.lastname: Mullooly
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nyante
authors.affiliation: Independent contractor, CT(ASCP), MB(ASCP), Stamford, CT, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Cora
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Carter
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Degnim
authors.affiliation: Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.affiliation: Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Medical School, Teviot Place, Edinburgh, UK.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Department of Epidemiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D012307:Risk Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D012739:Gonadal Steroid Hormones; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Breast cancer; Crown-like structures; Estrogens; Hormones; Postmenopausal