与癌症相关的疲劳是一种常见、繁重且常常得不到充分治疗的症状。迫切需要更有针对性的疲劳治疗。因此，我们检查了生物标志物和临床因素，以确定具有潜在不同病理生理学的疲劳亚型。研究人群包括德国一项基于人群的病例对照研究中的无病乳腺癌幸存者，他们在诊断后平均 6 年（FU1，n = 1871）和 11 年（FU2，n = 1295）进行重新评估。在 FU1 和 FU2，我们通过 20 项多维疲劳评估问卷和结构化电话访谈进一步评估疲劳程度。分析 FU1 收集的血清样本中的 IL-1ß、IL-2、IL-4、IL-6、IL-10、TNF-a、GM-CSF、IL-5、VEGF-A、SAA、CRP、VCAM- 1、ICAM-1、瘦素、脂联素和抵抗素。对 FU1 疲劳且无抑郁史的幸存者进行探索性聚类分析，得出三个聚类（CL1、CL2 和 CL3）。 CL1 (n = 195) 平均具有高水平的 TNF-α、IL1-β、IL-6、抵抗素、VEGF-A 和 GM-CSF，并且表现出高 BMI 和疼痛水平。 CL1中的疲劳更多地表现在身体维度上。相反，CL2（n = 78）的特点是瘦素水平高，认知疲劳程度最高。 CL3（n = 318）没有表现出任何显着的特征。与没有抑郁症的幸存者相比，有抑郁症病史的疲劳幸存者 (n = 214) 的身体、情绪和认知疲劳程度显着更高，并且从 FU1 到 FU2 的疲劳改善效果显着较差。总之，从广泛的表型“癌症相关疲劳”中，我们能够描绘出以生物标志物或抑郁症病史为特征的亚组。未来的研究可能会考虑这些亚型，最终实现更好的针对性疲劳治疗。© 2023 作者。约翰·威利出版的《国际癌症杂志》

Cancer-related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease-free breast cancer survivors of a German population-based case-control study who were re-assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20-item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone-interviews. Serum samples collected at FU1 were analyzed for IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-a, GM-CSF, IL-5, VEGF-A, SAA, CRP, VCAM-1, ICAM-1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF-α, IL1-β, IL-6, resistin, VEGF-A and GM-CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype "cancer-related fatigue" we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.