{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:47:24Z","timestamp":1791478044180,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,20]],"date-time":"2012-12-20T00:00:00Z","timestamp":1355961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>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\u2010treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long\u2010term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy\u2010exposed breast cancer survivors to those of a population\u2010based sample of women without a history of cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental design<\/jats:title><jats:p>Diffusion tensor imaging (DTI) MRI (1.5 T) was performed in 187 CMF (cyclophosphamide, methotrexate, and 5\u2010flourouracil) chemotherapy\u2010exposed 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\u2010matched cancer\u2010free reference subjects from a population\u2010based cohort study. Outcome measures were whole\u2010brain microstructural integrity as measured by fractional anisotropy and mean\/axial\/radial diffusivity and focal white matter integrity, which was analyzed with tract\u2010based spatial statistics. All analyses were adjusted for age, cardiovascular risk factors, education, and symptoms of depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Principal observations<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This cross\u2010sectional study suggests that among chemotherapy\u2010exposed breast cancer survivors white matter microstructural integrity deteriorates with accumulating time since treatment. This warrants further investigation. Hum Brain Mapp 35:889\u2013899, 2014. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hbm.22221","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T00:19:15Z","timestamp":1356135555000},"page":"889-899","source":"Crossref","is-referenced-by-count":107,"title":["Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy"],"prefix":"10.1002","volume":"35","author":[{"given":"Vincent","family":"Koppelmans","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam The Netherlands"},{"name":"Department of Psychosocial Research &amp; Epidemiology, Netherlands Cancer Institute\/Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"de Groot","sequence":"additional","affiliation":[{"name":"Department of Radiology, Erasmus MC, University 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