title: Circulating sex hormones and terminal duct lobular unit involution of the normal breast.
abstract: BACKGROUND
  Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011).
  
  
  METHODS
  We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Ptrends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.
  
  
  RESULTS
  Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72-0.89; Ptrend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; Ptrend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts.
  
  
  CONCLUSIONS
  These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.
  
  
  CONCLUSIONS
  Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. Cancer Epidemiol Biomarkers Prev; 23(12); 2765-73. ©2014 AACR.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Zeina G
authors.initials: ZG
authors.lastname: Khodr
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland. Division of Cancer Prevention, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.affiliation: George Washington University School of Medicine and Health Sciences, Washington, DC.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Linville
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Daphne
authors.initials: D
authors.lastname: Papathomas
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Clare
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Mies
authors.affiliation: Applied Molecular Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Anna Maria V
authors.initials: AM
authors.lastname: Storniolo
authors.affiliation: Computer Science and Electrical Engineering Department, University of Maryland, Baltimore, Maryland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Rosebrock
authors.affiliation: National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Jesus J
authors.initials: JJ
authors.lastname: Caban
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland. FigueroaJ@mail.nih.gov.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000033:anatomy & histology* / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin