title: Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy.
abstract: BACKGROUND
  Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis.
  
  
  METHODS
  One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm(2)) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses).
  
  
  RESULTS
  Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95% CI: 1.47, 4.42).
  
  
  CONCLUSIONS
  Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. clara.bodelon@nih.gov.|Division of Cancer Epidemiology and Genetics, 9609 Medical Center Dr., Rm 7-E236, Bethesda, MD, 20892, USA. clara.bodelon@nih.gov.
authors.forename: Clara
authors.initials: C
authors.lastname: Bodelon
authors.affiliation: Department of Pathology, John Hopkins University School of Medicine, Baltimore, MD, USA. cheaphy@jhmi.edu.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Heaphy
authors.affiliation: Departments of Pathology, Oncology and Urology, John Hopkins University School of Medicine, Baltimore, MD, USA. alan.meeker@gmail.com.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.affiliation: Department of Health Promotion Research, University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA. berta.geller@uvm.edu.
authors.forename: Berta
authors.initials: B
authors.lastname: Geller
authors.affiliation: Department of Biostatistics, University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Vacek
authors.affiliation: Department of Pathology, University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA. donald.weaver@uvm.edu.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.affiliation: Office of Health Promotion Research, University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA. rchicoin@uvm.edu.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Chicoine
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. John.Shepherd@ucsf.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Shepherd
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA. pmahmoudzadeh@gmail.com.
authors.forename: Amir Pasha
authors.initials: AP
authors.lastname: Mahmoudzadeh
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. deesha.patel@nih.gov.
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. brintonl@exchange.nih.gov.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA. shermanm@exchange.nih.gov.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. gierachg@mail.nih.gov.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
mesh_terms: D000328:Adult; D000368:Aged; D000071060:Breast Density; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D061705:Image-Guided Biopsy; D007962:Leukocytes / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*