• chemotherapy;
  • adjuvant;
  • breast neoplasms;
  • time;
  • diffusion tensor imaging;
  • magnetic resonance imaging;
  • brain;
  • axons


To date, only four small studies have investigated the effects of adjuvant chemotherapy for breast cancer on the microstructure of cerebral white matter with magnetic resonance imaging (MRI). These studies, which were conducted shortly up to 10 years post-treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long-term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy-exposed breast cancer survivors to those of a population-based sample of women without a history of cancer.

Experimental design

Diffusion tensor imaging (DTI) MRI (1.5 T) was performed in 187 CMF (cyclophosphamide, methotrexate, and 5-flourouracil) chemotherapy-exposed breast cancer survivors, mean age 64.2 (sd = 6.5) years, who had been diagnosed with cancer on average 21.2 (sd = 4.4) years before, and 374 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were whole-brain microstructural integrity as measured by fractional anisotropy and mean/axial/radial diffusivity and focal white matter integrity, which was analyzed with tract-based spatial statistics. All analyses were adjusted for age, cardiovascular risk factors, education, and symptoms of depression.

Principal observations

No significant group differences were observed in white matter integrity. However, within the breast cancer survivors, time since treatment was inversely associated with lower global and focal white matter integrity.


This cross-sectional study suggests that among chemotherapy-exposed breast cancer survivors white matter microstructural integrity deteriorates with accumulating time since treatment. This warrants further investigation. Hum Brain Mapp 35:889–899, 2014. © 2012 Wiley Periodicals, Inc.