Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking

Abstract

PURPOSE: This study examined the association of post-treatment changes in cognitive performance, apolipoprotein E (APOE), and smoking in breast cancer patients treated with adjuvant therapy. PARTICIPANTS AND METHODS: Breast cancer patients treated with chemotherapy (N = 55, age = 51.9 ± 7.1, education = 15.7 ± 2.6) were evaluated with a battery of neuropsychological tests prior to chemotherapy and at 1, 6, and 18 months post-chemotherapy. Matched groups of breast cancer patients not exposed to chemotherapy (N = 68, age = 56.8 ± 8.3, education = 14.8 ± 2.2) and healthy controls (N = 43, age = 53.0 ± 10.1, education = 15.2 ± 2.6) were evaluated at similar intervals. APOE epsilon 4 carrier status (APOE4+) and smoking history were also evaluated. RESULTS: The detrimental effect of APOE4+ genotype on post-treatment cognitive functioning was moderated by smoking history, that is, patients without a smoking history had significantly lower performance on measures of processing speed and working memory compared with those with a smoking history and healthy controls. Exploratory analyses revealed that APOE4+ patients without a smoking history who were exposed to chemotherapy showed a decline in performance in processing speed, compared with patients with a smoking history. A similar but less pronounced pattern was seen in the no chemotherapy group (primarily endocrine treatment). For working memory, the APOE4+ by smoking interaction was observed in the no chemotherapy group only. CONCLUSIONS: The association between APOE status, breast cancer treatment, and cognitive functioning was moderated by smoking history suggesting that both chemotherapy and endocrine therapy interact with APOE status and smoking to influence cognition. A putative mechanism is that smoking corrects a deficit in nicotinic receptor functioning and dopamine levels in APOE4+ individuals.