Cancer-related fatigue is a frequent, burdensome and often insufficiently treatedsymptom. A more targeted treatment of fatigue is urgently needed. Therefore, weexamined biomarkers and clinical factors to identify fatigue subtypes with potentiallydifferent pathophysiologies. The study population comprised disease-free breast can-cer 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 FatigueAssessment 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 andresistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no his-tory of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n=195) on aver-age had high levels of TNF-α, IL1-β, IL-6, resistin, VEGF-A and GM-CSF, and showedhigh 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 cogni-tive fatigue. CL3 (n=318) did not show any prominent characteristics. Fatigued sur-vivors with a history of depression (n=214) had significantly higher physical,emotional and cognitive fatigue and showed significantly less amelioration of fatiguefrom FU1 to FU2 than survivors without depression. In conclusion, from the broadphenotype“cancer-related fatigue”we were able to delineate subgroups character-ized by biomarkers or history of depression. Future investigations may take thesesubtypes into account, ultimately enabling a better targeted therapy of fatigue.
