title: Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study.
abstract: An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/- taxanes +/- endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/- taxanes +/- endocrine treatment (=BC + SYST; n = 26) compared to no systemic treatment (BC; n = 23) and no-cancer controls (NC; n = 30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/- endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/- endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC + SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.|Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Menning
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.|Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.affiliation: Department of Psychiatry, VU University Medical Center, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Neuro-Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.affiliation: Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.
authors.forename: Hester S A
authors.initials: HSA
authors.lastname: Oldenburg
authors.affiliation: Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands. s.schagen@nki.nl.
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D066127:White Matter / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Breast cancer; CRCI; Cancer related cognitive impairment; Chemotherapy; Cognition; Diffusion tensor imaging (DTI); Neurotoxicity; Side effects; White matter