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Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

Original publication

DOI

10.1016/j.molonc.2015.02.003

Type

Journal article

Journal

Mol Oncol

Publication Date

06/2015

Volume

9

Pages

1186 - 1193

Keywords

Breast cancer, Genome instability, Prognosis, Telomere, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Breast Neoplasms, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Survival Rate, Telomere, Telomere Homeostasis