Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome
Menée sur des patientes atteintes d'un cancer du sein, cette étude évalue l'association entre l'expression de la télomérase, la longueur des télomères et la réponse à un traitement adjuvant
INTRODUCTION:Telomere 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. Methods: qPCR 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. Results: Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors, and long telomere length was seen more often in tumors with detectable telomerase. 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 (HR=3.15; 95%CI: 1.34-7.40) and disease recurrence (HR=2.04; 95%CI: 0.96-4.30) 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. Conclusions: Telomerase modified the effect of endocrine therapy on breast cancer survivals, suggesting that telomerase may serve as a marker to guide the selection of adjuvant treatment for breast cancer.
Breast Cancer Research , article en libre accès, 2010