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

Cognitive effects of breast cancer anti-estrogen 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 60+ with non-metastatic breast cancer enrolled in the prospective Thinking and Living with Cancer study who underwent endocrine therapy had lower subjective (P=.06) and objective (P=.08) cognitive function than frequency-matched controls across time. At 5-years, however, women with breast cancer exposed to endocrine therapy and APOE4 carriers in particular exhibited lower learning and memory scores than other groups (p<.05). Our results suggest endocrine therapy may have long-term effects on cognitive function in women with breast cancer, particularly APOE4 carriers. Further characterization of genetic risk for long-term cognitive decline will be useful to inform survivorship care of older women.