Epidemiology

Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 1099-1106

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

  • Vincent KoppelmansAffiliated withDepartment of Epidemiology, Erasmus MC University Medical CenterDepartment of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital
  • , Michiel B. de RuiterAffiliated withDepartment of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalDepartment of Radiology, Academic Medical Center, University of Amsterdam
  • , Fedde van der LijnAffiliated withDepartment of Radiology, Erasmus MC University Medical CenterDepartment of Medical Informatics, Biomedical Imaging Group Rotterdam, Erasmus MC University Medical Center
  • , Willem BoogerdAffiliated withDepartment of Neuro-oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital
  • , Caroline SeynaeveAffiliated withDepartment of Medical Oncology, Erasmus MC University Medical Center-Daniel den Hoed Cancer Center
  • , Aad van der LugtAffiliated withDepartment of Radiology, Erasmus MC University Medical Center
  • , Henri VroomanAffiliated withDepartment of Radiology, Erasmus MC University Medical CenterDepartment of Medical Informatics, Biomedical Imaging Group Rotterdam, Erasmus MC University Medical Center
  • , Wiro J. NiessenAffiliated withDepartment of Radiology, Erasmus MC University Medical CenterDepartment of Medical Informatics, Biomedical Imaging Group Rotterdam, Erasmus MC University Medical CenterImaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology
  • , Monique M. B. BretelerAffiliated withDepartment of Epidemiology, Erasmus MC University Medical CenterGerman Center for Neurodegenerative diseases (DZNE)Institute for Medical Biometry, Informatics and Epidemiology, University Bonn Email author 
    • , Sanne B. SchagenAffiliated withDepartment of Psychosocial Research and Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Email author 

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Abstract

A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it is unclear if non-CNS chemotherapy is associated with long-term structural brain changes. We compared focal and total brain volume (TBV) of a large set of non-CNS directed chemotherapy-exposed breast cancer survivors, on average 21 years post-treatment, to that of a population-based sample of women without a history of cancer. Structural MRI (1.5T) was performed in 184 chemotherapy-exposed breast cancer patients, mean age 64.0 (SD = 6.5) years, who had been diagnosed with cancer on average 21.1 (SD = 4.4) years before, and 368 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were: TBV and total gray and white matter volume, and hippocampal volume. In addition, voxel based morphometry was performed to analyze differences in focal gray matter. The chemotherapy-exposed breast cancer survivors had significantly smaller TBV (−3.5 ml, P = 0.019) and gray matter volume (−2.9 ml, P = 0.003) than the reference subjects. No significant differences were observed in white matter volume, hippocampal volume, or local gray matter volume. This study shows that adjuvant chemotherapy for breast cancer is associated with long-term reductions in TBV and overall gray matter volume in the absence of focal reductions. The observed smaller gray matter volume in chemotherapy-exposed survivors was comparable to the effect of almost 4 years of age on gray matter volume reduction. These volume differences might be associated with the slightly worse cognitive performance that we observed previously in this group of breast cancer survivors.

Keywords

Long-term Survivors Breast cancer Adjuvant chemotherapy Brain volume MRI