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Telomere content correlates with stage and prognosis in breast cancer

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

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.

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Acknowledgments

This work was supported by research grants DAMD17-01-1-0572 and W81XWH-05-1-0226 to JKG from the DOD BCRP. CAF and CMH were supported by predoctoral training awards, DAMD 17-00-1-0370 and W81XWH-05-1-0273 from the DOD BCRP. JLW and CMH also were supported by an NIH MBRS Award, R25 GM60201, an NIH MARC Award, T34 GM08751, and DOD BCRP Undergraduate Breast Cancer Summer Research Training Program Award, DAMD17-02-1-0513-01. RNB and KBB and data from the HEAL Study were supported by SEER/NCI N01-CN-65034-29. We are indebted to Dr Melanie Royce for critically␣reviewing the manuscript and her several helpful suggestions.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA

    Colleen A. Fordyce, Christopher M. Heaphy, Marco Bisoffi, Jessica L. Wyaco & Jeffrey K. Griffith

  2. Department of Pathology, 1 University of New Mexico, Albuquerque, NM, USA

    Nancy E. Joste

  3. Department of Internal Medicine, 1 University of New Mexico, Albuquerque, NM, USA

    Aroop Mangalik & Richard N. Baumgartner

  4. New Mexico Tumor Registry, University of New Mexico School of Medicine, 1 University of New Mexico, Albuquerque, NM, USA

    Kathy B. Baumgartner & William C. Hunt

Authors
  1. Colleen A. Fordyce
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  2. Christopher M. Heaphy
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  3. Marco Bisoffi
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  4. Jessica L. Wyaco
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  5. Nancy E. Joste
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  6. Aroop Mangalik
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  7. Kathy B. Baumgartner
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  8. Richard N. Baumgartner
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  9. William C. Hunt
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  10. Jeffrey K. Griffith
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Corresponding author

Correspondence to Jeffrey K. Griffith.

Additional information

Colleen A. Fordyce and Christopher M. Heaphy contributed equally to this study

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Fordyce, C.A., Heaphy, C.M., Bisoffi, M. et al. Telomere content correlates with stage and prognosis in breast cancer. Breast Cancer Res Treat 99, 193–202 (2006). https://doi.org/10.1007/s10549-006-9204-1

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  • DOI: https://doi.org/10.1007/s10549-006-9204-1

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