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Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
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Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
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Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
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Journal Article
Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
2025
Overview
Background
Apolipoprotein Ɛ4 genotype (APOE4) has been associated with cancer-related cognitive impairment, but its interaction with treatments remains unclear. This longitudinal study aims to evaluate the association between APOE4 and cognitive impairment in women with breast cancer (BC) undergoing chemotherapy (CT) or endocrine therapy (ET).
Findings
Patients with stage I–III breast cancer completed cognitive tests at diagnosis (before surgery), then at year-1, year-2, and year-4 post-diagnosis. APOE4 status (APOE4+ [carriers] vs. APOE4− [non-carriers]) was genotyped from blood sample. Cognitive outcomes included episodic memory, working memory, attention, processing speed, and executive functions. Patients were defined as having overall cognitive impairment if ≥ 2 domains were impaired. We fitted logistic and linear mixed models to assess associations of APOE4 status with cognitive impairment over time and interactions of APOE4 with CT and ET. Among 334 patients, 64 (19%) were APOE4+, 117 (35%) patients were treated with CT, 41 (12%) with ET, and 162 (49%) with CT+ET. There were no significant association between overall cognitive impairment and APOE4, nor interactions with CT or ET. At year-4, APOE4+ patients treated with ET had lower attention performance than APOE4− patients not treated with ET, and APOE4+ patients not treated with ET had lower episodic memory performance than APOE4− patients not treated with ET.
Conclusions
This study suggests APOE4 genotyping is ineffective for detecting cognitive impairment in BC. New genotypes should be identified to predict cognitive decline in BC.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Aged
/ Antineoplastic Agents, Hormonal - adverse effects
/ Antineoplastic Agents, Hormonal - therapeutic use
/ Antineoplastic Combined Chemotherapy Protocols - adverse effects
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ APOE4
/ Apolipoprotein E4 - genetics
/ Biomedical and Life Sciences
/ Breast Neoplasms - complications
/ Breast Neoplasms - drug therapy
/ Cancer
/ Cancer-related cognitive impairment
/ Cognitive Dysfunction - etiology
/ Cognitive Dysfunction - genetics
/ Female
/ Genotype
/ Humans
/ Memory
/ Oncology
/ Smoking
