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Shortening of Leukocyte Telomeres Associated With Increased All-Cause and Breast Cancer–Specific Mortality in Breast Cancer Patients

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Key Points

  • Telomere shortening between baseline and 30 months was associated with increased risk of breast cancer-specific and all-cause mortality.
  • Over full follow-up, there were no significant associations of baseline or 30-month telomere lengths with mortality.

Short telomeres are associated with increased risk of cancer, but data on telomere length and mortality in breast cancer survivors are inconsistent. In a study reported in the Journal of the National Cancer Institute, Duggan et al found that decreases in telomere length between baseline and 30 months after diagnosis were associated with significantly increased all-cause and breast cancer–specific mortality. However, no association with mortality was found for baseline or 30-month telomere length.

In the study, peripheral blood leukocyte telomere length was measured in a multiethnic, prospective cohort of stage I to stage IIIA breast cancer survivors diagnosed between 1995 and 1999 (Health Eating Activity and Lifestyle study) with a median follow-up of 11.2 years. Telomere lengths at baseline (mean of 6 months after diagnosis, n = 611) and 30 months after diagnosis (n = 478) and the change between baseline and 30 months (n = 478) were examined for association with breast cancer–specific and all-cause mortality using Cox proportional hazards models adjusted for potential confounders.

There were 135 deaths in the cohort, with 74 due to breast cancer. Age was negatively correlated with baseline telomere length. Telomeres were longer at both baseline and 30 months in black women vs other racial/ethnic groups adjusted for age, and participants with higher levels of stress had shorter telomeres at both baseline and 30 months. Between baseline and 30 months, telomere length increased in 32.2% of patients and decreased in 67.8%.

Significant Effect of Telomere Shortening

There was no significant association between baseline telomere length and either all–cause mortality (hazard ratio [HR] = 0.83, P = .08) or breast cancer-specific mortality (HR = 0.88, P = .34). Similarly, there was no association between 30-month telomere length and either all-cause (HR = 0.78, P = .10) or disease-specific mortality (HR = 0.86, P = .44).

Patients with telomeres that shortened between baseline and 30 months had significantly increased risk of both breast cancer–specific (HR = 3.03, P = .03) and all-cause mortality (HR = 2.38, P = .006) compared with patients with telomeres that increased in length.

Results With Censoring at 5 Years

When follow-up was censored at 5-years after diagnosis, telomere length at baseline (HR = 0.66, P = .03) and at 30 months (HR = 0.51, P = .03) had significant inverse association with overall mortality; although the associations with breast cancer–specific mortality had similar effect sizes, they were not statistically significant (HR = 0.69, P = .08, for baseline length; HR = 0.57, P = .11, for 30-month length). Shortening of telomere length between baseline and 30 months was associated with significantly increased all-cause mortality (HR = 3.45, P = .03) and nonsignificantly increased breast cancer–specific mortality (HR = 2.46, P = .19).

For patients with estrogen receptor–negative tumors, longer telomere length at 30 months was associated with decreased risk of both breast cancer–specific and all-cause mortality compared with patients with estrogen receptor–positive tumors, but the differences did not remain significant after adjustment for multiple testing.

The investigators concluded, “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.”

Catherine Duggan, PhD, of Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the National Cancer Institute, National Institutes of Health, University of New Mexico, National Institute of Child Health and Human Development, and California Department of Health Services. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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