Abstract Background With improved survival in early breast cancer (EBC), attention is increasingly shifting toward long-term treatment sequelae. Chemotherapy-associated cognitive impairment (CICI or ‘chemobrain’) affects up to one-third of survivors yet remains under-recognized in routine care. Systemic treatments may induce structural and functional brain changes, particularly in regions linked to attention, memory, and executive function. Identifying vulnerable treatment regimens and patient profiles is crucial for tailoring survivorship care. This study aims to characterize the cognitive phenotype and neuroimaging correlates of CICI in EBC patients treated with anthracycline and/or taxane-based regimens, integrating cognitive assessments, longitudinal follow-ups, and multimodal brain MRI. Methods 328 patients who had completed anthracycline and/or taxane chemotherapy within the previous 12 months, along with 94 healthy volunteers, were enrolled from UK sites. Baseline and follow up evaluations assessing executive function, processing speed, attention, working and visuospatial memory were performed using an artificial intelligence-driven digital platform. Patients were followed up digitally every 3 months until 12 months post chemotherapy initiation. 18 patients with poorer performance and 19 age-matched controls underwent 3T brain MRI and in-person neuropsychological evaluation at Imperial College London. MRI scans were analysed using Region of Interest (ROI) and Voxel-Based Morphometry (VBM) to assess grey matter volumes and surface areas. Results At 12 months post-chemotherapy initiation, 27.3% breast cancer participants exhibited cognitive decline, 45.4% remained stable, and 27.3% showed fluctuations compared to baseline. Exploratory treatment-stratified observations revealed that cognitive decline at 12 months was more common with paclitaxel, especially without targeted therapies, while fluctuations in cognition were more frequent in patients receiving Epirubicin Cyclophosphamide + Docetaxel + Trastuzumab or Letrozole. The 18 patients selected for MRI were scanned on average 14.1 months post-chemotherapy; most patients had completed cytotoxic therapy and 89% were receiving endocrine therapy. MRI volumetric analysis revealed significant reductions in grey matter volume and surface area in left isthmus cingulate, orbitofrontal cortex, temporal pole, lingual gyrus, and precuneus - regions critically involved in working memory, semantic processing, attention, and visuospatial integration. Voxel-based analysis also showed reductions in cingulate, medial frontal, parietal, and periventricular areas. These were associated with lower Mini Mental State Examination scores and impairments in semantic and verbal fluency. Conclusions The Chemobrain preliminary data reveals objective cerebral morphological changes and cognitive impairment following anthracycline-taxane chemotherapy in a substantial number of patients at 12 months. However, long-term effects are yet to be determined. This underscores the urgent need to investigate chemotherapy-induced cognitive impairment in a larger cohort of patients to establish risk factors, preventive strategies and novel therapeutic approaches. Citation Format: L. Kenny, R. Vicidomini, L. McLeavy, P. Riddle, S. Cleator, E. Staples, P. Gayani, P. Edison. Does chemotherapy for early breast cancer affect cognition and brain structure? The Chemobrain Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-18.
Kenny et al. (Tue,) studied this question.