Chemotherapy for breast cancer is likely to cause structural brain changes, particularly in the hippocampus, which plays a key role in memory. Alterations in hippocampal subfields have not been fully described. This study aims to investigate changes in hippocampal subfield volumes in Breast cancer patients before and after chemotherapy, compared to healthy controls. Nineteen patients with breast cancer were evaluated before adjuvant therapy (T1), at one month (T2), and at one-year post-chemotherapy (T3). Healthy controls (n=23) underwent assessments at T1 and T3. Episodic memory retrieval and hippocampal subfield volumes were quantified using high-resolution proton density-weighted images segmented with HippUnfold software. Mixed-model analyses compared hippocampal volume changes at T1 between patients and healthy controls, longitudinally within the patient group (T1, T2, T3), and between the patient group and HC (T1, T3). Associations between memory retrieval scores and hippocampal subfield volumes were evaluated using general linear models. Across all assessments, patients performed worse than healthy controls. Subiculum volume was higher in patients compared to healthy controls at T1. No significant difference in memory abilities and hippocampal volume was found after chemotherapy compared to either before nor to the control group. No association between subfield volumes and episodic memory retrieval scores was observed. The effects are linked to cancer rather than chemotherapy, as no hippocampal volume changes or memory decline occurred post-treatment. Larger subiculum volume may be the result of neuroinflammation. Episodic memory deficits, independent of chemotherapy, suggest cancer-related cognitive impairment and could involved other brain regions or mechanisms.

Background and Purpose: Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are next generation therapy (NGT) administered with androgen deprivation therapy to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment have been recently reported. Experimental Approach: We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ during 5 days per week for six consecutive weeks. After behavioral tests, brain and plasma were collected for immunohistochemical studies. Spontaneous activity, cognitive functions and emotional reactivity, as well as neurobiological functions were investigated. Key Results: ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH+-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus, highlighted ENZ-induced dopaminergic regulation whithin the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory or behavioral flexibility performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN+-neurons in the dorsal hippocampus. Conclusion and Implications: These results establish the consequences of the mCRPC treatment ENZ in aged castrated mouse motivation to exploration and cognition, of particular importance for future management of patients elderly postrate cancer patients and their QoL.