Abstract
IntroductionTelomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis.MethodsqPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality.ResultsTelomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy.ConclusionsOverall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy.
Highlights
Telomere length plays important roles in maintaining genome stability and regulating cell replication and death
Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% confidential interval (CI): 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status
Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes
Summary
Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis. Telomeres are repeated sequences of oligonucleotides (TTAGGG) located at the ends of chromosomes, and have important functions in regulating cell replication and maintaining genome integrity [1,2,3]. Up-regulated telomerase activity and telomere elongation may increase drug resistance in breast and colorectal cancer cell lines [17,24]. Telomerase inhibitors can increase cancer cell death when used in combination with DNA-damaging anticancer drugs [25]. The purpose of this study was to investigate the possible effects of telomerase expression and telomere length on breast cancer treatment outcomes
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