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

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) u...

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Main Authors: Mylène Duivon, François Christy, Emilie Thomas, Justine Lequesne, Hélène Castel, Catherine Gaudin, Dominique Delmas, Sandrine Boyault, Olivier Rigal, Chayma Bousrih, Christelle Lévy, Florence Lerebours, Antonio Di Meglio, Patricia A. Ganz, Kathleen Van Dyk, Ines Vaz Luis, Marie Lange, Florence Joly
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-01974-2
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author Mylène Duivon
François Christy
Emilie Thomas
Justine Lequesne
Hélène Castel
Catherine Gaudin
Dominique Delmas
Sandrine Boyault
Olivier Rigal
Chayma Bousrih
Christelle Lévy
Florence Lerebours
Antonio Di Meglio
Patricia A. Ganz
Kathleen Van Dyk
Ines Vaz Luis
Marie Lange
Florence Joly
author_facet Mylène Duivon
François Christy
Emilie Thomas
Justine Lequesne
Hélène Castel
Catherine Gaudin
Dominique Delmas
Sandrine Boyault
Olivier Rigal
Chayma Bousrih
Christelle Lévy
Florence Lerebours
Antonio Di Meglio
Patricia A. Ganz
Kathleen Van Dyk
Ines Vaz Luis
Marie Lange
Florence Joly
author_sort Mylène Duivon
collection DOAJ
description 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.
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spelling doaj-art-c1845664d8ab4087b5e3ff2e1f6eb4bc2025-08-20T02:15:07ZengBMCBreast Cancer Research1465-542X2025-02-012711710.1186/s13058-025-01974-2Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal studyMylène Duivon0François Christy1Emilie Thomas2Justine Lequesne3Hélène Castel4Catherine Gaudin5Dominique Delmas6Sandrine Boyault7Olivier Rigal8Chayma Bousrih9Christelle Lévy10Florence Lerebours11Antonio Di Meglio12Patricia A. Ganz13Kathleen Van Dyk14Ines Vaz Luis15Marie Lange16Florence Joly17ANTICIPE U1086 INSERM-UCN, Equipe Labellisée Ligue Contre le Cancer, Centre François Baclesse, Normandie Université UNICAENANTICIPE U1086 INSERM-UCN, Equipe Labellisée Ligue Contre le Cancer, Centre François Baclesse, Normandie Université UNICAENPlateforme de Génomique des Cancers, Centre de Recherche en Cancérologie de Lyon CRCL, INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1ANTICIPE U1086 INSERM-UCN, Equipe Labellisée Ligue Contre le Cancer, Centre François Baclesse, Normandie Université UNICAENServices Unit PLATON, Cancer and Cognition Platform, University of Caen NormandyUNICANCERUNICANCERPlateforme de Génomique des Cancers, Centre de Recherche en Cancérologie de Lyon CRCL, INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Care Support Department, Centre Henri BecquerelGustave RoussyInstitut Normand du Sein, Centre François BaclesseMedical Oncology Department, Institut CurieCancer Survivorship Group, INSERM U981, Gustave Roussy FR Department for the Organization of Patient Pathways, Gustave RoussyDivision of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of CaliforniaDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los AngelesCancer Survivorship Group, INSERM U981, Gustave Roussy FR Department for the Organization of Patient Pathways, Gustave RoussyANTICIPE U1086 INSERM-UCN, Equipe Labellisée Ligue Contre le Cancer, Centre François Baclesse, Normandie Université UNICAENANTICIPE U1086 INSERM-UCN, Equipe Labellisée Ligue Contre le Cancer, Centre François Baclesse, Normandie Université UNICAENAbstract 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.https://doi.org/10.1186/s13058-025-01974-2Breast cancerAPOE4Cancer-related cognitive impairmentEndocrine therapyChemotherapy
spellingShingle Mylène Duivon
François Christy
Emilie Thomas
Justine Lequesne
Hélène Castel
Catherine Gaudin
Dominique Delmas
Sandrine Boyault
Olivier Rigal
Chayma Bousrih
Christelle Lévy
Florence Lerebours
Antonio Di Meglio
Patricia A. Ganz
Kathleen Van Dyk
Ines Vaz Luis
Marie Lange
Florence Joly
Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
Breast Cancer Research
Breast cancer
APOE4
Cancer-related cognitive impairment
Endocrine therapy
Chemotherapy
title Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
title_full Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
title_fullStr Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
title_full_unstemmed Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
title_short Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study
title_sort interaction between apoe e4 status chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors the canto cog longitudinal study
topic Breast cancer
APOE4
Cancer-related cognitive impairment
Endocrine therapy
Chemotherapy
url https://doi.org/10.1186/s13058-025-01974-2
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