title: Dense and nondense mammographic area and risk of breast cancer by age and tumor characteristics.
abstract: BACKGROUND
  Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages <55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes.
  
  
  METHODS
  Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression.
  
  
  RESULTS
  DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; P(trend) <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; P(trend) <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (P(trend) < 0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER(+) versus ER(-) tumors (P(het) = 0.02), while NDA was more strongly associated with decreased risk of ER(-) versus ER(+) tumors (P(het) = 0.03).
  
  
  CONCLUSIONS
  DA and NDA have differential associations with ER(+) versus ER(-) tumors that vary by age.
  
  
  CONCLUSIONS
  DA and NDA are important to consider when developing age- and subtype-specific risk models.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bertrand
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Scott
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jensen
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.affiliation: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Norman
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.affiliation: Department of Radiology, University of California, San Francisco, California.
authors.forename: John
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: Department of Pathology, University of California, San Francisco, California.
authors.forename: Yunn-Yi
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Radiology, University of California, San Francisco, California.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Wu
authors.affiliation: Department of Medicine, University of California, San Francisco, California.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.affiliation: Departments of Epidemiology and Biostatistics and General Internal Medicine Section, Department of Veterans Affairs, University of California, San Francisco, California.
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
authors.affiliation: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota. vachon.celine@mayo.edu.
authors.forename: Celine M
authors.initials: CM
authors.lastname: Vachon
mesh_terms: D000328:Adult; D000367:Age Factors; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D011859:Radiography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human