Altered Brain Functional Networks in Patients With Breast Cancer After Different Cycles of Neoadjuvant Chemotherapy

Abstract

Background: Cancer-related cognitive impairment (CRCI) impacts breast cancer (BC) patients' quality of life after chemotherapy. While recent studies have explored its neural correlates, single time-point designs cannot capture how these changes evolve over time. Purpose: To investigate changes in the brain connectome of BC patients at several time points during neoadjuvant chemotherapy (NAC). Study Type: Longitudinal. Subjects: 55 participants with BC underwent clinical assessments and fMRI at baseline (TP1), the first cycle of NAC (TP2, 30 days later), and the end (TP3, 140 days later). Two matched female healthy control (HCs, n = 20 and n = 18) groups received the same assessments. Field Strength/Sequence: rs-fMRI (gradient-echo EPI) and 3D T1-weighted magnetization-prepared rapid gradient echo sequence at 3.0 T. Assessment: Brain functional networks were analyzed using graph theory approaches. We analyzed changes in brain connectome metrics and explored the relationship between these changes and clinical scales (including emotion and cognitive test). Patients were divided into subgroups according to clinical classification, chemotherapy regimen, and menopausal status. Longitudinal analysis was performed at three time points for each subgroup. Statistical Tests: An independent sample t-test for patient-HC comparison at TP1. Analysis of variance and paired t-test for longitudinal changes. Regression analysis for relations between network measurements changes and clinical symptom scores changes. Significance was defined as p < 0.05. Results: Post-NAC, BC patients showed increased global efficiency (TP2-TP1 = 0.087, TP3-TP1 = 0.078), decreased characteristic path length (TP2-TP1 = −0.413, TP3-TP1 = −0.312), and altered nodal centralities mainly in the frontal-limbic system and cerebellar cortex. These abnormalities expanded with chemotherapy progression significantly (TP2 vs. TP3). Topological parameters changes were also correlated with clinical scales changes significantly. No differences were found within or between HC groups (p = 0.490–0.989) or BC subgroups (p = 0.053–0.988) at TP1. Data Conclusions: NAC affects the brain functional connectome of BC patients at TP2, and these changes persist and further intensify at TP3. Level of Evidence: 2. Technical Efficacy: Stage 5.