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Telomere DNA Content Predicts Breast Cancer–Free Survival Interval

Authors' Affiliations: ¹ Department of Biochemistry and Molecular Biology and ² Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico

Requests for reprints: Jeffrey K. Griffith, Department of Biochemistry and Molecular Biology, MSC08 4670, 1 University of New Mexico, Albuquerque, NM 87131-0001. Phone: 505-272-8432; Fax: 505-272-6587; E-mail: jkgriffith{at}salud.unm.edu.

Background: Telomeres are nucleoprotein complexes that protect chromosome ends from degradation and recombination. Critically shortened telomeres generate genomic instability. It has been postulated that the extent of telomere DNA loss is related to the degree of genomic instability within a tumor and therefore may presage clinical outcome. The objective of this investigation was to evaluate the hypothesis that telomere DNA content (TC) in breast tumor tissues predicts breast cancer–free survival interval.

Materials and Methods: Slot blot titration assay was used to quantitate TC in 530 archival breast tumor tissues in a population-based cohort. The relationships between TC, 12 risk factors for breast cancer adverse events (i.e., death due to breast cancer, breast cancer recurrence, or development of a new primary breast tumor), and breast cancer–free survival interval were evaluated by Fisher's exact test, log-rank analysis, and univariate and multivariate Cox proportional hazards models.

Results: TC was independent of each of the 12 risk factors. Ethnicity, tumor-node-metastasis stage, estrogen receptor, progesterone receptor, and p53 status, chemotherapy sequence, adjuvant therapy, and TC each conferred significant relative hazards. The best overall multivariate Cox proportional hazards model included TC, p53 status, tumor-node-metastasis stage, and estrogen receptor status as independent predictors of breast cancer–free survival interval (P < 0.00005). Low TC (200% of standard), relative to the high-TC group (>200% of standard), conferred an adjusted relative hazard of 2.88 (95% confidence interval, 1.16-7.15; P = 0.022) for breast cancer–related adverse events.

Conclusions: TC in breast cancer tissue is an independent predictor in this group of breast cancer–free survival interval.

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