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. 2025 Feb 19;27(1):25.
doi: 10.1186/s13058-025-01974-2.

Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study

Mylène Duivon  1 , François Christy  1   2 , Emilie Thomas  3   4 , Justine Lequesne  1   2   5 , Hélène Castel  5   6   7 , Catherine Gaudin  8 , Dominique Delmas  8 , Sandrine Boyault  3   4 , Olivier Rigal  9   10 , Chayma Bousrih  11 , Christelle Lévy  12 , Florence Lerebours  13 , Antonio Di Meglio  14 , Patricia A Ganz  15 , Kathleen Van Dyk  16 , Ines Vaz Luis  14 , Marie Lange  17   18   19 , Florence Joly  1   2   5
Affiliations

Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study

Mylène Duivon et al. Breast Cancer Res. .

Abstract

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.

Keywords: APOE4; Breast cancer; Cancer-related cognitive impairment; Chemotherapy; Endocrine therapy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All participants provided written informed consent and the study was approved by the ethics committee (ID-RCB:2011-A01095-36,11-039). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart
Fig. 2
Fig. 2
Percentage of patients with an overall cognitive impairment and impaired cognitive domain according to APOE4 status. Note: no significant difference was observed
Fig. 3
Fig. 3
Cognitive changes according to APOE4 and ET status (linear mixed models. *: p value < 0.05). Note: models were adjusted for age (< 50, 50–70, > 70 years old), level of education (< 10 years, 10-12 years, > 12 years), smoking status (ever, never), menopausal status, chemotherapy, and cognition at baseline
See this image and copyright information in PMC

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