title: Neurotoxicity in breast cancer survivors ≥10 years post-treatment is dependent on treatment type.
abstract: Adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on brain function and structure. However, little is known about neurotoxicity of specific treatment regimens. To compare neurotoxicity profiles after different treatment strategies, we used neurocognitive testing and multimodality MRI in BC survivors randomized to high-dose (HI), conventional-dose (CON-) CT or radiotherapy (RT) only and a healthy control (HC) group. BC survivors who received CON-CT (n = 20) and HC (n = 20) were assessed using a neurocognitive test battery and multimodality MRI including 3D-T1, Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy (1H-MRS) to measure various aspects of cerebral white (WM) and gray matter (GM). Data were compared to previously assessed groups of BC survivors who received HI-CT (n = 17) and RT-only (n = 15). Testing took place on average 11.5 years post-CT. 3D-T1 showed focal GM volume reductions both for HI-CT and CON-CT compared to RT-only (p < .004). DTI-derived mean diffusivity and 1H-MRS derived N-acetyl aspartate showed WM injury specific to HI-CT but not CON-CT (p < .05). Residual effects were revealed in the RT-only group compared to HC on MRI and neurocognitive measurements (p < .05). Ten years after adjuvant CT for BC lower cerebral GM volume was found in HI as well as CON-CT BC survivors whereas injury to WM is restricted to HI-CT. This might indicate that WM brain changes after BC treatment may show more pronounced (partial) recovery than GM. Furthermore, our results suggest residual neurotoxicity in the RT-only group, which warrants further investigation.
authors.affiliation: Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Myrle M
authors.initials: MM
authors.lastname: Stouten-Kemperman
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.forename: Vincent
authors.initials: V
authors.lastname: Koppelmans
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D056324:Diffusion Tensor Imaging; D004305:Dose-Response Relationship, Drug; D005260:Female; D066128:Gray Matter / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D009483:Neuropsychological Tests; D009929:Organ Size; D066244:Proton Magnetic Resonance Spectroscopy; D017741:Survivors; D066127:White Matter / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects