title: Case-control study of mammographic density and breast cancer risk using processed digital mammograms.
abstract: Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care.
  
  
  
  We conducted a case-control study nested among non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were aged 40 to 74 years and had screening mammograms acquired on Hologic FFDM machines. Cases (n = 297) were women with a first invasive breast cancer diagnosed after a screening FFDM. For each case, up to five controls (n = 1149) were selected, matched on age and year of FFDM and image batch number, and who were still under follow-up and without a history of breast cancer at the age of diagnosis of the matched case. Percent density (PD) and dense area (DA) were assessed by a radiological technologist using Cumulus. Conditional logistic regression was used to estimate odds ratios (ORs) for breast cancer associated with PD and DA, modeled continuously in standard deviation (SD) increments and categorically in quintiles, after adjusting for body mass index, parity, first-degree family history of breast cancer, breast area, and menopausal hormone use.
  
  
  
  Median intra-reader reproducibility was high with a Pearson's r of 0.956 (range 0.902 to 0.983) for replicate PD measurements across 23 image batches. The overall mean was 20.02 (SD, 14.61) for PD and 27.63 cm(2) (18.22 cm(2)) for DA. The adjusted ORs for breast cancer associated with each SD increment were 1.70 (95 % confidence interval, 1.41-2.04) for PD, and 1.54 (1.34-1.77) for DA. The adjusted ORs for each quintile were: 1.00 (ref.), 1.49 (0.91-2.45), 2.57 (1.54-4.30), 3.22 (1.91-5.43), 4.88 (2.78-8.55) for PD, and 1.00 (ref.), 1.43 (0.85-2.40), 2.53 (1.53-4.19), 2.85 (1.73-4.69), 3.48 (2.14-5.65) for DA.
  
  
  
  PD and DA measured using Cumulus on processed FFDM images are positively associated with breast cancer risk, with similar magnitudes of association as previously reported for film-screen mammograms. Processed digital mammograms acquired for routine clinical care in a general practice setting are suitable for breast density and cancer research.
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA. laurel.habel@kp.org.|Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA. laurel.habel@kp.org.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jafi A
authors.initials: JA
authors.lastname: Lipson
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA.
authors.forename: Ninah
authors.initials: N
authors.lastname: Achacoso
authors.affiliation: Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Rothstein
authors.affiliation: Departments of Medical Biophysics and Medical Imaging, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.|Smarter Imaging Program, Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Yaffe
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Rhea Y
authors.initials: RY
authors.lastname: Liang
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Acton
authors.affiliation: Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.affiliation: Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Rubin
authors.affiliation: Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Weiva
authors.initials: W
authors.lastname: Sieh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology*; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D018426:SEER Program; D044465:White People
keywords: Breast cancer; Epidemiology; Mammographic density; Mammography; Risk factors