title: Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Psychosocial Research & Epidemiology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Koppelmans
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003430:Cross-Sectional Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D056324:Diffusion Tensor Imaging / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D056784:Leukoencephalopathies / Q000139:chemically induced / Q000473:pathology*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017741:Survivors; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate
keywords: adjuvant; axons; brain; breast neoplasms; chemotherapy; diffusion tensor imaging; magnetic resonance imaging; time