Telomere content correlates with stage and prognosis in breast cancer

Breast Cancer Res Treat. 2006 Sep;99(2):193-202. doi: 10.1007/s10549-006-9204-1. Epub 2006 Jun 3.

Abstract

Purpose: To evaluate the hypothesis that telomere DNA content (TC) in breast tumor tissue correlates with TNM staging and prognosis.

Experimental design: Slot blot assay was used to quantitate TC in 70 disease-free normal tissues from multiple organ sites, and two independent sets of breast tumors containing a total of 140 samples. Non-parametric Rank-Sums tests, logistic regression and Cox proportional hazards models were used to evaluate the relationships between TC and tumor size, nodal involvement, TNM stage, 5-year survival and disease-free interval.

Results: TC in 95% of normal tissues was 75-143% of that in the placental DNA standard, whereas only 50% of tumors had TC values in this range. TC was associated with tumor size (p=0.02), nodal involvement (p<0.0001), TNM stage (p=0.004), 5-year overall survival (p=0.0001) and 5-year disease-free survival (p=0.0004). A multivariable Cox model was developed using age at diagnosis, TNM stage and TC as independent predictors of breast cancer-free survival. Relative to the high TC group (>123% of standard), low TC (<101% of standard) conferred an adjusted relative hazard of 4.43 (95% CI 1.4-13.6, p=0.009). Receiver operating characteristic curves using thresholds defined by the TC distribution in normal tissues predicted 5-year breast cancer-free survival with 50% sensitivity and 95% specificity, and predicted death due to breast cancer with 75% sensitivity and 70% specificity.

Conclusions: TC in breast cancer tissue is an independent predictor of clinical outcome and survival interval, and may discriminate by stage.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology
  • DNA, Neoplasm / analysis*
  • Disease-Free Survival
  • Female
  • Humans
  • Mastectomy
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Survival Rate
  • Telomere / genetics*

Substances

  • DNA, Neoplasm