Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Simpson, Katherine, Jones, R. E., Grimstead, Julia W., Hills, Robert Kerrin ORCID: https://orcid.org/0000-0003-0166-0062, Pepper, Christopher John and Baird, Duncan Martin ORCID: https://orcid.org/0000-0001-8408-5467 2015. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients. Molecular Oncology 9 (6) , pp. 1186-1193. 10.1016/j.molonc.2015.02.003

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	Breast cancer; Prognosis; Genome instability; Telomere
Additional Information:	Published online 6 February 2015
Publisher:	Elsevier
ISSN:	1574-7891
Funders:	Cancer Research UK
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	June 2015
Last Modified:	06 Jan 2024 03:34
URI:	https://orca.cardiff.ac.uk/id/eprint/72919

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