Tim A Ahles1, Irene Orlow2, Elizabeth Schofield3, Yuelin Li3, Elizabeth Ryan3, James C Root3, Sunita K Patel4, Katrazyna McNeal3, Alexandra Gaynor3, Heidi Tan4, Vani Katheria4, Jessica Vazquez4, Sergio Corrales-Guerrero2, Keimya Sadeghi2, Tiffany Traina5, Arti Hurria6. 1. Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ahlest@mskcc.org. 2. Molecular Epidemiology Laboratory, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Departments of Population Science and Supportive Care Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 5. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Center for Cancer and Ageing, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Abstract
PURPOSE: This study aims to determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance but that smoking history would decrease the negative effect of ε4 on cognition. METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 328) and age and education matched non-cancer controls (N = 162) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected, and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. RESULTS: After adjusting for age, cognitive reserve, depression, and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. CONCLUSIONS: The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors, and disease history in determining cognitive function. IMPLICATIONS FOR CANCER SURVIVORS: These results help explain why only a subset of breast cancer survivors appear to be vulnerable to cognitive problems.
PURPOSE: This study aims to determine whether older breast cancer survivors score lower on neuropsychological tests compared to matched non-cancer controls and to test the hypotheses that survivors who were APOE ε4 carriers would have the lowest cognitive performance but that smoking history would decrease the negative effect of ε4 on cognition. METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 328) and age and education matched non-cancer controls (N = 162) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological and psychological assessments. Blood for APOE genotyping was collected, and smoking history was assessed at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or no chemotherapy and approximately 50% had a smoking history. RESULTS: After adjusting for age, cognitive reserve, depression, and fatigue, breast cancer survivors scored significantly lower on all domains of cognitive function. A significant two-way interaction demonstrated that the negative effect of ε4 on cognitive performance was stronger among survivors. A significant three-way interaction supported the hypothesis that smoking history had a protective effect on cognitive function in ε4 carriers that was more pronounced in the controls than the survivors. CONCLUSIONS: The results support the long-term cognitive impact of breast cancer diagnosis and treatments on older, disease-free survivors, particularly for ε4 carriers. The results also emphasize the importance of assessing smoking history when examining APOE and cognition and are an example of the complex interactions of age, genetics, health behaviors, and disease history in determining cognitive function. IMPLICATIONS FOR CANCER SURVIVORS: These results help explain why only a subset of breast cancer survivors appear to be vulnerable to cognitive problems.
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