title: Influence of patterns of hormone replacement therapy use and mammographic density on breast cancer detection.
abstract: BACKGROUND
  There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer.
  
  
  METHODS
  This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression.
  
  
  RESULTS
  A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined HRT.
  
  
  CONCLUSIONS
  Information on mammographic density and HRT use should routinely be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening.
authors.affiliation: Division of Preventive Oncology, Cancer Care Ontario, 620 University Avenue, Toronto, Ontario, Canada M5G 2L7. anna_chiarelli@cancercare.on.ca
authors.forename: Anna M
authors.initials: AM
authors.lastname: Chiarelli
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Kirsh
authors.forename: Neil S
authors.initials: NS
authors.lastname: Klar
authors.forename: Rene
authors.initials: R
authors.lastname: Shumak
authors.forename: Roberta
authors.initials: R
authors.lastname: Jong
authors.forename: Eve
authors.initials: E
authors.lastname: Fishell
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Yaffe
authors.forename: Norman F
authors.initials: NF
authors.lastname: Boyd
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology*; D016022:Case-Control Studies; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D011374:Progesterone / Q000627:therapeutic use; D011372:Progestins / Q000627:therapeutic use; D012107:Research Design; D012307:Risk Factors; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D004967:Estrogens; D011372:Progestins; D011374:Progesterone