title: Analysis of terminal duct lobular unit involution in luminal A and basal breast cancers.
abstract: BACKGROUND
  Involution of terminal duct lobular units (TDLUs), the structures that give rise to most breast cancers, has been associated with reduced breast cancer risk. Data suggest that the etiology and pathogenesis of luminal A and core basal phenotype (CBP) breast cancers differ, but associations with TDLU involution are unknown. Accordingly, we performed a masked microscopic assessment of TDLU involution in benign tissues associated with luminal A and CBP breast cancers diagnosed among women less than age 55 years.
  
  
  METHODS
  Cases were participants in a population-based case-control study conducted in Poland. Increased TDLU involution was defined as fewer acini per TDLU or shorter TDLU diameter. Luminal A was defined as estrogen receptor (ER) positive and/or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER2) negative and CBP as negative for ER, PR, and HER2 with expression of basal cytokeratins or epidermal growth factor receptor (EGFR). We performed logistic regression to evaluate associations between TDLU involution and tumor subtypes, adjusted for clinical characteristics and breast cancer risk factors.
  
  
  RESULTS
  Among 232 luminal A and 49 CBP cancers associated with evaluable TDLUs, CBP tumors were associated with significantly greater average number of acini per TDLU (odds ratio (OR) = 3.36, 95% confidence interval (CI) = 1.36 to 8.32, P = 0.009) and larger average TDLU diameter (OR = 2.49, 95% CI = 1.08 to 5.74, P = 0.03; comparing highest to lowest group, adjusted for age and study site).
  
  
  CONCLUSIONS
  We suggest that TDLU involution is less marked in benign tissues surrounding CBP as compared to luminal A cancers, which may reflect differences in the etiology and pathogenesis of these tumor subtypes.
authors.affiliation: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. royang@mail.nih.gov
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Louise
authors.initials: L
authors.lastname: Brinton
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; C508053:ERBB2 protein, human