International Journal of Clinical Oncology

, Volume 24, Issue 1, pp 68–77 | Cite as

Long-term influence of adjuvant breast radiotherapy on cognitive function in breast cancer patients treated with conservation therapy

  • Osamu Shibayama
  • Kazuhiro Yoshiuchi
  • Masatoshi Inagaki
  • Yutaka Matsuoka
  • Eisho Yoshikawa
  • Yuriko Sugawara
  • Tatsuo Akechi
  • Noriaki Wada
  • Shigeru Imoto
  • Koji Murakami
  • Asao Ogawa
  • Yosuke UchitomiEmail author
Original Article



The mechanisms underlying cognitive decline after radiotherapy not directed at brain areas remains unclear. We previously suggested that adjuvant breast radiotherapy in breast conservation therapy could lower memory function soon after therapy, and that the process might be partially mediated by plasma interleukin (IL)-6 levels. The present study investigated how that relationship changes longitudinally.


We performed the Wechsler Memory Scale-Revised (WMS-R) test and measured plasma IL-6 levels for 47 breast cancer surgical patients within 1 year after the initial therapy (study 1) and more than 2 years after study 1 (study 2). We also performed 2 × 2 mixed [the radiotherapy group (n = 25) or the no-radiotherapy group (n = 22) × study 1 or study 2] analysis of covariance on the WMS-R indices and plasma IL-6 levels. The association between changes in plasma IL-6 levels and changes in the WMS-R indices between the two studies was evaluated using Pearson’s correlation coefficient.


The Immediate Verbal Memory Index was significantly higher in study 2. The Delayed Recall Index was significantly higher in study 2 and significantly lower in the radiotherapy group only in study 1. There was a significant correlation between changes in plasma IL-6 levels and changes only in the Delayed Recall Index of the WMS-R.


Memory decline in breast cancer patients soon after adjuvant breast radiotherapy was restored approximately 3 years after treatment, and decreased plasma IL-6 levels might be involved in the recovery process.


Radiotherapy Cognitive decline Interleukin-6 Breast cancer Longitudinal study 



This study was supported by a third-term Comprehensive Control Research for Cancer Grant from the Japanese Ministry of Health, Labor, and Welfare; by a Grant from the Japanese Ministry of Education, Culture, Science, and Technology; and by the National Cancer Center Research and Development Fund. The funding sources had no involvement in the study design, data collection, data analysis, data interpretation, writing the report, or the decision to submit the paper for publication. The authors thank Ms. Nobue Taguchi, Yuko Kojima, Yukiko Kozaki, and Ryoko Katayama for their research assistance. We also express special thanks to all participants in the study.


This study was supported by a third-term Comprehensive Control Research for Cancer Grant and Research for Promotion of Cancer Control Programmes (H26-political-general-002) from the Japanese Ministry of Health, Labor, and Welfare; by a Grant from the Japanese Ministry of Education, Culture, Science, and Technology; and by the National Cancer Center Research and Development Fund (27-A).

Compliance with ethical standards

Conflict of interest

Author Uchitomi Y. received research grants from the Japanese Ministry of Health, Labour and Welfare for the submitted work. Author Inagaki M. declares that he has received grants from The Ministry of Health, Labour and Welfare, Japan, the Ministry of Education, Science, and Technology, Japan, Novartis Pharma, and Okayama Health Foundation. Author Inagaki M. received lecture fees from Pfizer Japan Inc., Mochida Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Daiichi-Sankyo Co., Ltd., Meiji Seika Pharma Co. Ltd., and Takeda Pharmaceutical Co., Ltd. outside the submitted work. Author Inagaki M. received royalties from Nippon Hyoron Sha Co., Ltd., Nanzando Co., Ltd., Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., and Technomics, Inc., outside the submitted work. Author Matsuoka Y. received lecture fees from Morinaga Milk Industry Co. Ltd., Eli Lilly Japan K. K., and Takeda Pharmaceutical Company Ltd.

Ethical approval

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

Informed consent

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


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Copyright information

© Japan Society of Clinical Oncology 2018

Authors and Affiliations

  • Osamu Shibayama
    • 1
  • Kazuhiro Yoshiuchi
    • 2
  • Masatoshi Inagaki
    • 3
  • Yutaka Matsuoka
    • 4
  • Eisho Yoshikawa
    • 5
  • Yuriko Sugawara
    • 6
  • Tatsuo Akechi
    • 7
  • Noriaki Wada
    • 8
  • Shigeru Imoto
    • 9
  • Koji Murakami
    • 10
  • Asao Ogawa
    • 11
  • Yosuke Uchitomi
    • 12
    Email author
  1. 1.Department of Psychosomatic Internal MedicineYokohama-Rosai HospitalYokohamaJapan
  2. 2.Department of Stress Sciences and Psychosomatic Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan
  3. 3.Department of NeuropsychiatryOkayama University HospitalOkayamaJapan
  4. 4.Division of Health Care Research, Center for Public Health SciencesNational Cancer CenterTokyoJapan
  5. 5.Department of NeuropsychiatryNippon Medical SchoolTama cityJapan
  6. 6.NISSAN Motor Health Insurance SocietyYokohamaJapan
  7. 7.Department of Psychiatry and Cognitive-Behavior MedicineNagoya City University Graduate School of Medical SciencesNagoyaJapan
  8. 8.Department of General SurgeryTokyo Dental College Ichikawa General HospitalIchikawaJapan
  9. 9.Department of Breast SurgeryKyorin University HospitalMitakaJapan
  10. 10.Department of RadiologyJuntendo University School of MedicineTokyoJapan
  11. 11.Psycho-Oncology Division, Research Center for Innovative OncologyNational Cancer Center Hospital EastKshiwaJapan
  12. 12.Innovation Center for Supportive, Palliative, and Psychosocial CareNational Cancer CenterTokyoJapan

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