Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: a pilot longitudinal study
Older cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer.
Chemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60–82 years) with stage I–III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity, were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed.
In the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected = 0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected = 0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance.
Our study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer.
This study was funded by National Institutes of Health/National Institute on Aging Grants R03 AG045090-02 (BTC) and R01 AG037037-01A1 (Arti Hurria). Nancy Linford, PhD provided editing assistance.
BTC, SKP, and Arti Hurria designed and conducted the study. BTC prepared the manuscript. TJ performed rs-fMRI data analysis and correlative analysis. BTC, SKP, TJ, NY, HM, CWW, RR, JR, AIH, AS, TA, NP, WD contributed to interpretation and description of the data. TJ and HM performed statistical analysis. JM, JW, YY, MS, DL, MSS, JV, and VK contributed to study accrual and procedures. All authors approved the final manuscript. We dedicate this manuscript to the memory of Dr. Arti Hurria whose vision and support made this work possible.
Compliance with ethical standards
Conflict of interest
JM reports being a consultant/advisory role in the following entities: Puma and Pfizer. YY reports research grants from and being a consultant with an advisory role in the following entities: Puma, Novartis, Genentech, Merck, GTx, Pfizer, and Immunemedics, outside the submitted work. All other authors declare no competing interests.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the Institutional Review Board of City of Hope and with the 1964 Helsinki Declaration and its later amendments, as well as all local and national laws. This study is registered on ClinicalTrials.gov (NCT01992432).
Informed consent was obtained from all study participants in the study.
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