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Hermelink, Kerstin; Bühner, Markus; Sckopke, Philipp; Neufeld, Franziska; Kaste, Judith; Voigt, Varinka; Münzel, Karin; Wuerstlein, Rachel; Ditsch, Nina; Hellerhoff, Karin; Rjosk-Dendorfer, Dorothea; Braun, Michael; Koch, Franz Edler von; Härtl, Kristin; Hasmüller, Stephan; Bauerfeind, Ingo; Debus, Gerlinde; Herschbach, Peter; Mahner, Sven; Harbeck, Nadia (1. October 2017): Chemotherapy and Post-traumatic Stress in the Causation of Cognitive Dysfunction in Breast Cancer Patients. In: Journal of the National Cancer Institute, Vol. 109, No. 10
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Background Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress. Methods Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants—patients who did or did not receive chemotherapy and healthy control subjects—on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided. Results Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z-score: –0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year (T = –0.11, P = .02). Conclusions Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.