Breast Cancer Research and Treatment

, Volume 176, Issue 1, pp 181–189 | Cite as

Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: a pilot longitudinal study

  • Bihong T. ChenEmail author
  • Taihao Jin
  • Sunita K. Patel
  • Ningrong Ye
  • Huiyan Ma
  • Chi Wah Wong
  • Russell C. Rockne
  • James C. Root
  • Andrew J. Saykin
  • Tim A. Ahles
  • Andrei I. Holodny
  • Neal Prakash
  • Joanne Mortimer
  • James Waisman
  • Yuan Yuan
  • Daneng Li
  • Mina S. Sedrak
  • Jessica Vazquez
  • Vani Katheria
  • William Dale
Clinical trial



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.

Author contributions

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.

Ethical approval

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 (NCT01992432).

Informed consent

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Bihong T. Chen
    • 1
    • 2
    Email author
  • Taihao Jin
    • 1
  • Sunita K. Patel
    • 3
  • Ningrong Ye
    • 1
  • Huiyan Ma
    • 2
  • Chi Wah Wong
    • 4
  • Russell C. Rockne
    • 5
  • James C. Root
    • 6
  • Andrew J. Saykin
    • 7
  • Tim A. Ahles
    • 6
  • Andrei I. Holodny
    • 8
  • Neal Prakash
    • 9
  • Joanne Mortimer
    • 10
  • James Waisman
    • 10
  • Yuan Yuan
    • 10
  • Daneng Li
    • 10
  • Mina S. Sedrak
    • 10
  • Jessica Vazquez
    • 2
  • Vani Katheria
    • 2
  • William Dale
    • 2
    • 11
  1. 1.Department of Diagnostic RadiologyCity of Hope National Medical CenterDuarteUSA
  2. 2.Center for Cancer and AgingCity of Hope National Medical CenterDuarteUSA
  3. 3.Department of Population ScienceCity of Hope National Medical CenterDuarteUSA
  4. 4.Center for InformaticsCity of Hope National Medical CenterDuarteUSA
  5. 5.Division of Mathematical OncologyCity of Hope National Medical CenterDuarteUSA
  6. 6.Neurocognitive Research LabMemorial Sloan Kettering Cancer CenterNew YorkUSA
  7. 7.Center for NeuroimagingIndiana University School of MedicineIndianapolisUSA
  8. 8.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  9. 9.Division of NeurologyCity of Hope National Medical CenterDuarteUSA
  10. 10.Department of Medical OncologyCity of Hope National Medical CenterDuarteUSA
  11. 11.Department of Supportive Care MedicineCity of Hope National Medical CenterDuarteUSA

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