title: Changes in brain activation in breast cancer patients depend on cognitive domain and treatment type.
abstract: BACKGROUND
  Cognitive problems in breast cancer patients are common after systemic treatment, particularly chemotherapy. An increasing number of fMRI studies show altered brain activation in breast cancer patients after treatment, suggestive of neurotoxicity. Previous prospective fMRI studies administered a single cognitive task. The current study employed two task paradigms to evaluate whether treatment-induced changes depend on the probed cognitive domain.
  
  
  METHODS
  Participants were breast cancer patients scheduled to receive systemic treatment (anthracycline-based chemotherapy +/- endocrine treatment, n = 28), or no systemic treatment (n = 24) and no-cancer controls (n = 31). Assessment took place before adjuvant treatment and six months after chemotherapy, or at similar intervals. Blood oxygen level dependent (BOLD) activation and performance were measured during an executive functioning task and an episodic memory task. Group-by-time interactions were analyzed using a flexible factorial design.
  
  
  RESULTS
  Task performance did not differ between patient groups and did not change over time. Breast cancer patients who received systemic treatment, however, showed increased parietal activation compared to baseline with increasing executive functioning task load compared to breast cancer patients who did not receive systemic treatment. This hyperactivation was accompanied by worse physical functioning, higher levels of fatigue and more cognitive complaints. In contrast, in breast cancer patients who did not receive systemic treatment, parietal activation normalized over time compared to the other two groups.
  
  
  CONCLUSIONS
  Parietal hyperactivation after systemic treatment in the context of stable levels of executive task performance is compatible with a compensatory processing account of hyperactivation or maintain adequate performance levels. This over-recruitment of brain regions depends on the probed cognitive domain and may represent a response to decreased neural integrity after systemic treatment. Overall these results suggest different neurobehavioral trajectories in breast cancer patients depending on treatment type.
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Menning
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Neuro-Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.affiliation: Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Hester S A
authors.initials: HS
authors.lastname: Oldenburg
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sanne B
authors.identifier: http://orcid.org/0000-0003-4848-8706
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000523:psychology* / Q000628:therapy; D016022:Case-Control Studies; D003071:Cognition; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008568:Memory; D008875:Middle Aged; D059906:Neuroimaging