Interaction of endocrine therapy for breast cancer with APOE4 status on cognition over 5-year follow-up

Sep 23, 2026

Uploaded by Angel

Cognitive effects of breast cancer antiestrogen endocrine therapy remain a key survivorship concern as evidence links estrogen to late-life dementia risk. APOE4 genotype has been associated with cognitive difficulties, largely studied in younger survivors. In women aged 60+ with nonmetastatic breast cancer in the Thinking and Living with Cancer study, those receiving endocrine therapy showed lower subjective and objective cognition versus controls over time. At 5 years, endocrine therapy and APOE4 carriers showed reduced learning and memory scores, suggesting long-term effects and the value of refining genetic risk for cognitive decline to guide older women’s survivorship care.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Abstract

Study population and design

Key findings over follow-up

Implications for survivorship care

JNCI Cancer Spectrum, 2026, 10(2), pkag028 [https://doi.org/10.1093/jncics/pkag028](https://doi.org/10.1093/jncics/pkag028) Advance Access Publication Date: March 17, 2026 Brief Communication Interaction of endocrine therapy for breast cancer with APOE4 status on cognition over 5-year follow-up Kathleen Van Dyk , PhD1,2, 3, 􀀃 , Wanting Zhai, MS4, Tim A. Ahles , PhD5, James C. Root , PhD5, Jaeil Ahn , PhD4, Ashley L. Artese , PhD6, 7, Traci N. Bethea , PhD8, Harvey J. Cohen, MD7, Martine Extermann , MD9, Deena Graham , MD10, Claudine Isaacs , MD11, Heather S.L. Jim , PhD11, Brenna C. McDonald , PsyD12, Zev M. Nakamura , MD13, Sunita K. Patel , PhD3, Kelly E. Rentscher , PhD14, Andrew J. Saykin , PsyD12, Brent J. Small , PhD15, Danielle B. Tometich , PhD16, Xingtao Zhou , MS4, Judith E. Carroll , PhD1, 17, Jeanne S. Mandelblatt , MD, MPH18 1Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States 2Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States 3City of Hope, Duarte, CA, United States 4Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC, United States 5Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, United States 6Department of Exercise Science and Health Promotion, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL, United States 7Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, United States 8Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States 9Senior Adult Oncology Program, Department of Oncology Sciences, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA 10John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, United States 11Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, United States 12Department of Radiology and Imaging Sciences, Melvin and Bren Simon Comprehensive Cancer Center, and Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, United States 13Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States 14Department of Psychiatry and Behavioral Medicine, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, United States 15School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States 16Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, United States 17Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Los Angeles, CA, United States 18Georgetown Lombardi Institute for Cancer and Aging Research (I-CARE), Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC, United States 􀀃 Corresponding author: Kathleen Van Dyk, PhD, Department of Supportive Care Medicine, City of Hope National Medical Center, 1500 E. Duarte Rd, Duarte, CA 91010, United States ([kvandyk@coh.org](kvandyk@coh.org)) . Abstract Cognitive effects of breast cancer antiestrogen endocrine therapy are a salient concern for survivors, given the growing evidence that estrogen plays a role in late-life dementia risk. The APOE4 genotype has been linked with risk for cognitive difficulties, studied mainly in younger cancer survivors. We found that women aged 60þ with nonmetastatic breast cancer enrolled in the prospective Thinking and Living with Cancer study who underwent endocrine therapy had lower subjective (P ¼ .06) and objective (P ¼ .08) cognitive function than frequency-matched controls across time. At 5 years, however, women with breast cancer exposed to endocrine therapy and APOE4 car

FAQs

Who was included in the study and what therapy exposure was assessed?

Women aged 60+ with nonmetastatic breast cancer enrolled in the Thinking and Living with Cancer study were assessed based on undergoing endocrine therapy versus frequency-matched controls.

How did endocrine therapy affect cognitive outcomes over time?

Endocrine therapy was associated with lower subjective and objective cognitive function compared with controls across time.

What did the 5-year results show specifically for APOE4 carriers?

At 5 years, women exposed to endocrine therapy who were APOE4 carriers exhibited lower learning and memory scores than other groups.

Sep 23, 2026

Uploaded by Angel