The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen.
Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment.



A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region.



Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance.



This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.
Xingui
X
Chen
Center for Biomedical Engineering, University of Science and Technology of China, Hefei, China.
Xiaoxuan
X
He
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Longxiang
L
Tao
Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Jingjing
J
Li
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Jiaonan
J
Wu
Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.|Department of Medical Psychology, Anhui Medical University, Hefei, China.
Chunyan
C
Zhu
Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.|Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Department of Medical Psychology, Anhui Medical University, Hefei, China.
Fengqiong
F
Yu
Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.|Department of Medical Psychology, Anhui Medical University, Hefei, China.
Lei
L
Zhang
Department of Breast Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Jingjie
J
Zhang
Center for Biomedical Engineering, University of Science and Technology of China, Hefei, China.
Bensheng
B
Qiu
Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.|Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Department of Medical Psychology, Anhui Medical University, Hefei, China.
Yongqiang
Y
Yu
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.|Collaborative Innovation Centre of Neuropsychiatric Disorders and Mental Health, Anhui Province, China.|Department of Medical Psychology, Anhui Medical University, Hefei, China.
Kai
K
Wang
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D001931:Brain Mapping; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D010100:Oxygen
breast cancer; endocrine therapy; functional connectivity; tamoxifen; working memory