title: Benign breast disease, mammographic breast density, and the risk of breast cancer.
abstract: BACKGROUND
  Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk.
  
  
  METHODS
  We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided.
  
  
  RESULTS
  Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses.
  
  
  CONCLUSIONS
  Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA 94143-0320, USA. jtice@medicine.ucsf.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tice
authors.forename: Ellen S
authors.initials: ES
authors.lastname: O'Meara
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.forename: Celine
authors.initials: C
authors.lastname: Vachon
authors.forename: Rachel
authors.initials: R
authors.lastname: Ballard-Barbash
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000473:pathology*; D001941:Breast Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D005348:Fibrocystic Breast Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D016017:Odds Ratio; D011159:Population Surveillance; D011230:Precancerous Conditions / Q000000981:diagnostic imaging / Q000473:pathology; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors