title: Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors.
abstract: BACKGROUND
  Progressive telomere shortening with cell division is a hallmark of aging. Short telomeres are associated with increased cancer risk, but there are conflicting reports about telomere length and mortality in breast cancer survivors.
  
  
  METHODS
  We measured peripheral blood leukocyte telomere length at two time points in women enrolled in a multiethnic, prospective cohort of stage I to stage IIIA breast cancer survivors diagnosed between 1995 and 1999 with a median follow-up of 11.2 years. We evaluated associations between telomere length measured at mean 6 (baseline; LTL0; n = 611) and 30 months (LTL30; n = 478) after diagnosis and the change between those time points (n = 478), with breast cancer-specific and all-cause mortality using Cox proportional hazards models adjusted for possible confounders. Statistical tests were two-sided.
  
  
  RESULTS
  There were 135 deaths, of which 74 were due to breast cancer. Neither baseline nor 30-month telomere length was associated with either all-cause or breast cancer-specific mortality (LTL0: hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.67 to 1.02; HR = 0.88; 95% CI = 0.67 to 1.15; LTL30: HR = 0.78, 95% CI = 0.59 to 1.05; HR = 0.86; 95% = CI = 0.58 to 1.26, respectively). However, participants whose telomeres shortened between baseline and 30 months were at a statistically significantly increased risk of breast cancer-specific (HR = 3.03; 95% CI = 1.11 to 8.18) and all-cause mortality (HR = 2.38; 95% CI = 1.28 to 4.39) compared with participants whose telomeres lengthened. When follow-up was censored at 5-years after diagnosis, LTL0 (HR = 0.66; 95% CI = 0.45 to 0.96), LTL30 (HR = 0.51; 95% CI = 0.29 to 0.92), and change in telomere length (HR = 3.45; 95% CI = 1.11 to 10.75) were statistically significantly associated with all-cause mortality.
  
  
  CONCLUSIONS
  Telomere shortening was associated with increased risk of breast cancer-specific and all-cause mortality, suggesting that change in blood telomere length over time could be a biomarker of prognosis. Research on determinants of telomere length and change is needed.
authors.affiliation: Affiliations of authors: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (CD, II, SH, AM); Department of Pathology (RR, DP, PR), Department of Epidemiology, School of Public Health (AM), and Department of Medicine, School of Medicine, University of Washington, Seattle, WA (RR, DP, PR, AM); Office of Cancer Survivorship (CA) and Applied Research Program (RB-B), National Cancer Institute/National Institutes of Health, Bethesda, MD; Department of Epidemiology & Population Health, University of Louisville, Louisville, KY (KB, RB); Department of Cancer Etiology, City of Hope National Medical Center, Duarte, CA (LB).
authors.forename: Catherine
authors.initials: C
authors.lastname: Duggan
authors.forename: Rosana
authors.initials: R
authors.lastname: Risques
authors.forename: Catherine
authors.initials: C
authors.lastname: Alfano
authors.forename: Donna
authors.initials: D
authors.lastname: Prunkard
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Imayama
authors.forename: Sarah
authors.initials: S
authors.lastname: Holte
authors.forename: Kathy
authors.initials: K
authors.lastname: Baumgartner
authors.forename: Rick
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Rachel
authors.initials: R
authors.lastname: Ballard-Barbash
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinovitch
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007962:Leukocytes; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data; D016615:Telomere / Q000473:pathology*; D059506:Telomere Shortening