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A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer

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Abstract

Some women report cognitive impairment after adjuvant chemotherapy (CTh) for breast cancer. Here we explore cognitive function, and underlying mechanisms with blood tests and functional magnetic resonance imaging (fMRI). Women treated for early breast cancer were recruited to three groups based on self-reported cognitive symptoms (CS) using FACT-Cog scores. CTh + CS+ (n = 44) had received chemotherapy and self-reported cognitive symptoms; CTh + CS- (n = 52) had chemotherapy but did not report cognitive problems; CTh- (n = 30) had not received chemotherapy. Clinical and computer-based neuropsychological tests were performed. Blood tests included 10 cytokines, sex hormones, coagulation factors, and apolipoprotein-E genotype. fMRI (n = 101) was performed while subjects performed an n-back memory task. Participants had median age 50 (range: 29–60) years and were a median of 17 months post-diagnosis. On clinical neuropsychological tests 19% had cognitive impairment using Global Deficit Score, and 36% using International Cancer and Cognition Task Force criteria with no significant differences in cognitive impairment rates between groups. CTh + CS+ had significantly more fatigue, anxiety/depression and poorer quality-of-life than other groups. There was no association between FACT-Cog and neuropsychological scores. There were significant differences in frontal and parietal regions on fMRI scans: CTh- showed hyperactivation compared to chemotherapy-treated groups, CTh + CS+ had more frontal activation than CTh + CS-. Elevated IL-1, IL-2 were associated weakly and IL-8 more strongly with neuropsychological impairment (rho > 0.20). There were no differences in global cognitive impairment between groups. Cognitive symptoms were associated with fatigue and anxiety/depression, but not with objective cognitive impairment. fMRI scans differed among the three groups.

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Acknowledgements

This study was supported by a developmental grant from the Canadian Breast Cancer Research Alliance, and expanded with support from the Susan G. Komen Breast Cancer Foundation. Dr. Janette Vardy is supported by a Practitioner Fellowship from the National Breast Cancer Foundation, Australia.

We thank Irene Chemerysnky and Alison Park for performing the neuropsychological testing, David Laurence and Jessica Zhang for data management, Hien Tran for assistance with MRI testing, and Drs Michiel de Ruiter, Taylor Schmitz and Kimberley Chiew for initial advice and assistance with fMRI imaging processing. We thank all the patients who participated in the study and acknowledge the assistance of the clinicians and clinical trial nurses.

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Authors and Affiliations

  1. Concord Cancer Centre, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW, 2137, Australia

    Janette L. Vardy

  2. Sydney Medical School, University of Sydney, Sydney, Australia

    Janette L. Vardy & Haryana M. Dhillon

  3. Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

    Janette L. Vardy, Anna Dodd & Ian F. Tannock

  4. Netherlands Cancer Institute, Amsterdam, The Netherlands

    Myrle M. Stouten-Kemperman

  5. McMaster University, Hamilton, Canada

    Gregory Pond

  6. Department of Oncology, Queen’s University, Kingston, Canada

    Christopher M. Booth

  7. St. Michael’s Hospital, University of Toronto, Toronto, Canada

    Sean B. Rourke

  8. Toronto Western Hospital, University of Toronto, Toronto, Canada

    Adrian Crawley

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  1. Janette L. Vardy
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  3. Gregory Pond
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Correspondence to Janette L. Vardy.

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Funding

This study was supported by a developmental grant from the Canadian Breast Cancer Research Alliance, and expanded with support from the Susan G. Komen Breast Cancer Foundation. Dr. Janette Vardy is supported by a Practitioner Fellowship from the National Breast Cancer Foundation, Australia.

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None of the authors have any conflicts of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Institute where work performed: Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

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Vardy, J.L., Stouten-Kemperman, M.M., Pond, G. et al. A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer. Brain Imaging and Behavior 13, 15–26 (2019). https://doi.org/10.1007/s11682-017-9728-5

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