Brouwers Barbara, Hatse Sigrid, Dal Lago Lissandra, Neven Patrick, Vuylsteke Peter, Dalmasso Bruna, Debrock Guy, Van Den Bulck Heidi, Smeets Ann, Bechter Oliver, Bailur Jithendra Kini, Kenis Cindy, Laenen Annouschka, Schöffski Patrick, Pawelec Graham, Journe Fabrice, Ghanem Ghanem-Elias, Wildiers Hans
Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Oncotarget. 2016 May 24;7(21):29977-88. doi: 10.18632/oncotarget.8796.
This prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on biological and clinical markers of aging and frailty.
Women ≥ 70 years old with early breast cancer were enrolled after surgery and assigned to a chemotherapy (Docetaxel and Cyclophosphamide) group (CTG, n=57) or control group (CG, n=52) depending on their planned adjuvant treatment. Full geriatric assessment (GA) and Quality of Life (QoL) were evaluated at inclusion (T0), after 3 months (T1) and at 1 year (T2). Blood samples were collected to measure leukocyte telomere length (LTL), levels of interleukin-6 (IL-6) and other circulating markers potentially informative for aging and frailty: Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), Insulin-like Growth Factor 1 (IGF-1), Monocyte Chemotactic Protein 1 (MCP-1) and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES).
LTL decreased significantly but comparably in both groups, whereas IL-6 was unchanged at T2. However, IL-10, TNF-α, IGF-1 and MCP-1 suggested a minor biological aging effect of chemotherapy. Clinical frailty and QoL decreased at T1 in the CTG, but recovered at T2, while remaining stable in the CG.
Chemotherapy (TC) is unlikely to amplify clinical aging or induce frailty at 1 year. Accordingly, there is no impact on the most established aging biomarkers (LTL, IL-6).
这项前瞻性观察性研究旨在评估辅助化疗对衰老和虚弱的生物学及临床标志物的影响。
年龄≥70岁的早期乳腺癌女性患者在术后入组，根据其计划的辅助治疗方案分为化疗组（多西他赛和环磷酰胺，CTG，n = 57）或对照组（CG，n = 52）。在入组时（T0）、3个月后（T1）和1年时（T2）进行全面的老年评估（GA）和生活质量（QoL）评估。采集血样以测量白细胞端粒长度（LTL）、白细胞介素-6（IL-6）水平以及其他可能对衰老和虚弱有指示意义的循环标志物：白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、胰岛素样生长因子1（IGF-1）、单核细胞趋化蛋白1（MCP-1）和正常T细胞激活后表达和分泌的调节因子（RANTES）。
两组的LTL均显著下降，但下降程度相当，而IL-6在T2时未发生变化。然而，IL-10、TNF-α、IGF-1和MCP-1提示化疗有轻微的生物学衰老效应。CTG组的临床虚弱和QoL在T1时下降，但在T2时恢复，而CG组则保持稳定。
化疗（TC）在1年内不太可能加剧临床衰老或导致虚弱。因此，对最常用的衰老生物标志物（LTL、IL-6）没有影响。
