title: Mammographic density and estrogen receptor status of breast cancer.
abstract: BACKGROUND
  The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)-positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer.
  
  
  METHODS
  We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity.
  
  
  RESULTS
  Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18).
  
  
  CONCLUSIONS
  Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure.
authors.affiliation: Department of Medicine, University of California at San Francisco, 1635 Divisadero Street, Suite 600, San Francisco, CA 04115, USA. eziv@itsa.ucsf.edu
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tice
authors.forename: Rebecca
authors.initials: R
authors.lastname: Smith-Bindman
authors.forename: John
authors.initials: J
authors.lastname: Shepherd
authors.forename: Steven
authors.initials: S
authors.lastname: Cummings
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D005260:Female; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000032:analysis*; D012042:Registries / Q000706:statistics & numerical data*; D012307:Risk Factors
chemical_list: D011960:Receptors, Estrogen