Alterations in Brain White Matter Tractography in Older Long-Term Breast Cancer Survivors Treated with Chemotherapy

<b>Purpose:</b> This study aimed to investigate alterations in brain white matter fiber bundle integrity among older long-term breast cancer survivors treated with chemotherapy, with a focus on identifying potential neural correlates of cancer-related cognitive impairment (CRCI). <b>Methods:</b> Women aged 65 years and older were prospectively enrolled and divided into three groups: breast cancer survivors 5 to 15 years after chemotherapy treatment (C+), breast cancer survivors without chemotherapy (C-), and age-sex-matched healthy controls (HC). Participants underwent brain MRI with diffusion tensor imaging and cognitive testing at time point 1 (TP1) upon enrollment and again after two years at time point 2 (TP2). White matter fiber tract integrity was assessed using fractional anisotropy-based (FA) tractography across 80 major fiber bundles in the brain. <b>Results:</b> Over the two-year period, both C+ and C- groups exhibited significant reductions in white matter integrity with FA reductions noted in several fiber tracts, including the left inferior fronto-occipital fasciculus (C+ group: <i>p</i> < 0.01; C- group: <i>p</i> = 0.01), right inferior fronto-occipital fasciculus (<i>p</i> < 0.01), left inferior longitudinal fasciculus (C+ group: <i>p</i> < 0.01; C- group: <i>p</i> = 0.04), right inferior longitudinal fasciculus (C+ group: <i>p</i> = 0.04; C- group: <i>p</i> = 0.02), right vertical occipital fasciculus (C+ group: <i>p</i> < 0.02; C- group: <i>p</i> = 0.01), left anterior corticostriatal tracts (C+ group: <i>p</i> < 0.01; C- group: <i>p</i> = 0.02), right anterior corticostriatal tracts (C+ group: <i>p</i> = 0.01; C- group: <i>p</i> = 0.02), anterior commissure (C+ group: <i>p</i> = 0.01; C- group: <i>p</i> = 0.03), and forceps minor (C+ group: <i>p</i> = 0.03; C- group: <i>p</i> = 0.01). In addition, FA reductions were noted in the left superior longitudinal fasciculus (<i>p</i> < 0.01), uncinate fasciculus (<i>p</i> = 0.01), thalamic radiation (<i>p</i> = 0.04), left optic radiations (<i>p</i> = 0.04) and right optic radiations (<i>p</i> = 0.03) in the C+ group only. No significant changes over time were detected in the HC group (<i>p</i> > 0.05). The fiber tract changes were considered statistically significant at a threshold of <i>p</i> < 0.05, with family-wise error (FWE) correction. Significant positive correlation was found between the longitudinal changes in the right inferior fronto-occipital fasciculus and the fluid composite cognition score in the C+ group (R = 0.65 and <i>p</i> = 0.03; Pearson's correlation). <b>Conclusions:</b> This study showed continued white matter fiber tract alterations in the older long-term breast cancer survivors who may have cognitive difficulties years after chemotherapy. Diffusion tensor imaging may provide valuable insights into the white matter microstructural correlates of CRCI in older cancer survivors.