title: Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis.
abstract: Women with high levels of mammographic density (MD) have a four- to six-fold increased risk of developing breast cancer; however, most neither have a prevalent tumor nor will they develop one. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is related to increased breast cancer risk. Correlations of microvessel density (MVD) in tissue, MD and biopsy diagnosis have not been defined, and we investigated these relationships among 218 women referred for biopsy.
  
  
  
  MVD was determined by counting CD31-positive vessels in whole sections of breast biopsies in three representative areas; average MVD was transformed to approximate normality. Using digital mammograms, we quantified MD volume with single X-ray absorptiometry. We used linear regression to evaluate associations between MVD and MD adjusted for age and body mass index (BMI) overall, and stratified by biopsy diagnosis: cases (in situ or invasive cancer, n = 44) versus non-cases (non-proliferative or proliferative benign breast disease, n = 174). Logistic regression adjusted for age, BMI, and MD was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between MVD and biopsy diagnosis. We also assessed whether the MVD-breast cancer association varied by MD.
  
  
  
  MVD and MD were not consistently associated. Higher MVD was significantly associated with higher odds of in situ/invasive disease (ORAdjusted = 1.69, 95 % CI = 1.17-2.44). MVD-breast cancer associations were strongest among women with greater non-dense volume.
  
  
  
  Increased MVD in tissues is associated with breast cancer, independently of MD, consistent with MRI findings suggestive of its possible value as a radiological cancer biomarker.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Felix.20@osu.edu.|Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Felix.20@osu.edu.|Present address: Division of Epidemiology, The Ohio State University College of Public Health, 1841 Neil Avenue, 300C Cunz Hall, Columbus, OH, 43210, USA. Felix.20@osu.edu.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Felix
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Lenz
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morris
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.affiliation: Department of Family Medicine, University of Vermont, Burlington, VT, USA.
authors.forename: Berta
authors.initials: B
authors.lastname: Geller
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Vacek
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.affiliation: Office of Health Promotion Research, University of Vermont, Burlington, VT, USA.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Chicoine
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Shepherd
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Amir Pasha
authors.initials: AP
authors.lastname: Mahmoudzadeh
authors.affiliation: University of California, San Francisco, CA, USA.|Present address: Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wang
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Serghei
authors.initials: S
authors.lastname: Malkov
authors.affiliation: Department of Radiology, University of Vermont, Burlington, VT, USA.
authors.forename: Sally D
authors.initials: SD
authors.lastname: Herschorn
authors.affiliation: Department of Diagnostic Radiology, Neuroradiology Section, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johnson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Renata L
authors.initials: RL
authors.lastname: Cora
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D000071060:Breast Density; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008327:Mammography; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012307:Risk Factors
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Angiogenesis; Breast neoplasms; Lesional density; Mammographic density; Pathology