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Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level

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Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.

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Fig. 1
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Fig. 4



Voxel Based Morphometry


Gray Matter


International Cancer and Cognition Task Force


Magnetic Resonance Imaging


Linear Mixed Model


Family-wise error


State-Trait Anxiety


Beck Depression Inventory – Short Form


Encoding, Storage, Retrieval


Battérie D’Efficience Mnésique


Trail Making Test


Likehood Ratio Test


Akaike Information Criterion


Bayesian Information Criterion


White Matter


Cerebro-spinal Fluid


Full Width at Half Maximum


Total intracranial volume


Mini Mental State Examination


Standard Deviation


Supplementary Motor Area


Montreal Neurological Institute


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Authors would like to thank the clinical research department of the Centre François Baclesse (Caen; Dr. Clarisse, Mrs. Rieux), the medical oncology department of the Centre François Baclesse (Dr Delcambre, Dr. Ollivier, Dr. Berthet, Dr. Segura and Dr. Swisters) for their help in patient recruitment, and the participants for their active contribution to these results.


This work was supported by the ARC foundation – for cancer research (2017–2020), the association “Ligue contre la cancer” (both national and Calvados department), the association “Cancer du sein, parlons en” (2011), and the Cancéropôle Nord-Ouest.

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Correspondence to Joy Perrier.

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Informed consent was obtained from all individual participants included in the study. All procedures performed in the current study that involved human participants were approved and in accordance with the local ethical standards research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Perrier, J., Viard, A., Levy, C. et al. Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level. Brain Imaging and Behavior 14, 226–241 (2020). https://doi.org/10.1007/s11682-018-9991-0

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  • Breast cancer
  • Cognition
  • Education level
  • Anxiety
  • Magnetic resonance imaging