title: Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort.
abstract: Atypical hyperplasia (AH) and mammographic breast density (MBD) are established risk factors for breast cancer (BC), but their joint contributions are not well understood. We examine associations of MBD and BC by histologic impression, including AH, in a sub﻿cohort of women from the Mayo Clinic Benign Breast Disease Cohort.
  
  
  
  Women with a diagnosis of BBD and mammogram between 1985 and 2001 were eligible. Histologic impression was assessed via pathology review and coded as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and AH. MBD was assessed clinically using parenchymal pattern (PP) or BI-RADS criteria and categorized as low, moderate or high. Percent density (PD) was also available for a subset of women. BC and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from date of benign biopsy to BC, death or last contact. Standardized incidence ratios (SIRs) compared the observed number of BCs to expected counts. Cox regression estimated multivariate-adjusted MBD hazard ratios.
  
  
  
  Of the 6271 women included in the study, 1132 (18.0%) had low MBD, 2921 (46.6%) had moderate MBD, and 2218 (35.4%) had high MBD. A total of 3532 women (56.3%) had NP, 2269 (36.2%) had PDWA and 470 (7.5%) had AH. Over a median follow-up of 14.3 years, 528 BCs were observed. The association of MBD and BC risk differed by histologic impression (p-interaction = 0.03), such that there was a strong MBD and BC association among NP (p < 0.001) but non-significant associations for PDWA (p = 0.27) and AH (p = 0.96). MBD and BC associations for AH women were not significant within subsets defined by type of MBD measure (PP vs. BI-RADS), age at biopsy, number of foci of AH, type of AH (lobular vs. ductal) and body mass index, and after adjustment for potential confounding variables. Women with atypia who also had high PD (>50%) demonstrated marginal evidence of increased BC risk (SIR 4.98), but results were not statistically significant.
  
  
  
  We found no evidence of an association between MBD and subsequent BC risk in women with AH.
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.affiliation: Department of Subspecialty General Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Degnim
authors.affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ethan P
authors.initials: EP
authors.lastname: Heinzen
authors.affiliation: Department of Health Sciences Research, Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Frank
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Winham
authors.affiliation: Department of Medical Oncology, Division of the Women's Cancer Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: Marlene H
authors.initials: MH
authors.lastname: Frost
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Scott
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jensen
authors.affiliation: Department of General Internal Medicine, Division of the Breast Diagnostic Clinic, Mayo Clinic, Rochester, MN, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Manduca
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Brandt
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Dana H
authors.initials: DH
authors.lastname: Whaley
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.affiliation: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Vachon.Celine@mayo.edu.
authors.forename: Celine M
authors.initials: CM
authors.lastname: Vachon
mesh_terms: D001706:Biopsy / Q000379:methods; D001940:Breast / Q000473:pathology*; D000071060:Breast Density / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology*; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors
keywords: Atypical hyperplasia; Breast cancer risk; Mammographic breast density