title: Very Late Treatment-Related Alterations in Brain Function of Breast Cancer Survivors.
abstract: Although adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on cognition and brain function, studies on adverse effects of specific treatment regimens are scarce. Here, neurotoxicity profiles after different treatment strategies were compared in BC survivors randomized to high-dose (HI) or conventional-dose (CON-) CT, in women treated with radiotherapy (RT) -only and a healthy control (HC) group. We administered a neurocognitive test battery, a planning fMRI task (Tower of London) and episodic memory fMRI task (Paired Associates paradigm) in BC survivors who received CON-CT (n=24) and HC (n=27). Data were compared to BC survivors who received HI-CT (n=17) and RT-only (n=15) and who were previously assessed. Testing took place ±11.5 years post-CT. Furthermore, neurocognitive data were compared to neurocognitive data acquired ≤2 years post-treatment. Cognitive assessment revealed sustained cognitive decline in 10.5% of HI-CT, 8.3% of CON-CT, 6.7% of RT-only patients and 0% in the HC. Hypoactivation was found in task-related prefrontal and parietal areas for both CT-groups versus RT-only, with HI-CT showing more pronounced hypoactivation than CON-CT, combined with worse task performance. RT-only survivors performed at a similar level to HC while showing hyperactivation in task-related brain areas. Long after treatment, CT is associated with cognitive problems and task-related hypoactivation that depend on the specific cytotoxic regimen. This worse performance in patients who received CT could be explained by impaired brain functioning that is more severe with more intense CT.
authors.affiliation: 1Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Division of Psychosocial Research and Epidemiology,Amsterdam,The Netherlands.
authors.forename: Myrle M
authors.initials: MM
authors.lastname: Stouten-Kemperman
authors.affiliation: 1Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Division of Psychosocial Research and Epidemiology,Amsterdam,The Netherlands.
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.affiliation: 3Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Department of Neuro-Oncology,Amsterdam,The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.affiliation: 4VU University Medical Center,Department of Anatomy and Neuroscience,Amsterdam,The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: 2Academic Medical Center,Department of Radiology,University of Amsterdam,The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.affiliation: 1Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,Division of Psychosocial Research and Epidemiology,Amsterdam,The Netherlands.
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001245:Association Learning; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D017741:Survivors; D014057:Tomography, X-Ray Computed
chemical_list: D010100:Oxygen
keywords: Adjuvant chemotherapy; Adverse effects; Breast cancer; Cognition; fMRI; long-term