title: Histologic changes in the breast with menopausal hormone therapy use: correlation with breast density, estrogen receptor, progesterone receptor, and proliferation indices.
abstract: OBJECTIVE
  This retrospective study systematically compared mammographic density with histology in women receiving or not receiving menopausal hormone therapy (HT).
  
  
  METHODS
  This study was approved by the institutional review board. Twenty-eight postmenopausal women using HT were matched with 28 postmenopausal women not using HT at the time of breast cancer diagnosis. Noncancerous tissue from mastectomy specimens was examined histologically to quantitate the content of fibrous stroma, ducts, and lobule types 1, 2, and 3. Tissue samples were also evaluated for estrogen receptor, progesterone receptor, and Ki67 activity in the ducts and lobules. Breast density was quantified by digitizing the contralateral mammogram and computer-assisted interactive thresholding.
  
  
  RESULTS
  High breast density in women using HT was correlated with greater fibrous stroma (P = 0.020) and lobule type 1 (P = 0.016). Breast density also correlated with Ki67 activity in the ducts (P = 0.031) and lobules (P= 0.023) for both groups combined. Estrogen and progesterone receptors did not correlate with either breast density or HT use.
  
  
  CONCLUSIONS
  Increased fibrous stroma and lobule type 1 are associated with increasing mammographic density in women using HT, independent of estrogen and progesterone receptor up-regulation. These findings suggest that increased breast density may be mediated through a paracrine effect. The increase in breast cancer risk with HT use may be due to an increase in target lobule type 1 cells.
authors.affiliation: Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA. jah7w@virginia.edu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Harvey
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Santen
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.forename: Viktor E
authors.initials: VE
authors.lastname: Bovbjerg
authors.forename: Mark E
authors.initials: ME
authors.lastname: Smolkin
authors.forename: Fathima S
authors.initials: FS
authors.lastname: Sheriff
authors.forename: Jose
authors.initials: J
authors.lastname: Russo
mesh_terms: D001940:Breast / Q000187:drug effects* / Q000473:pathology*; D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D019394:Ki-67 Antigen / Q000032:analysis; D008327:Mammography; D008875:Middle Aged; D017698:Postmenopause; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone