Elucidating the relationship between breast cancer and brain cortical structure: a Mendelian randomization study

Abstract Cancer-associated cognitive impairment is a significant challenge for individuals who have survived breast cancer, affecting their quality of life. In this study, we conducted an inaugural comprehensive Mendelian randomization analysis discerning the causal relationship between breast cancer, including its two subtypes, and the cerebral cortical structure. Our analysis indicated that estrogen receptor-negative breast cancer significantly decreased surface area (β = −593.01 mm2, 95% CI: −1134.9 to −51.1 mm2, P = 0.032). At the regional level, estrogen receptor-negative breast cancer showed a significant association with surface area and thickness in 17 cortical regions. These regions included the insula, posterior cingulate, superior frontal, precuneus, fusiform, lateral occipital, and rostral middle frontal. Specifically, estrogen receptor-negative breast cancer had a significant impact on decreasing the surface area of the insula without considering global weight (β = −14.09 mm2, 95% CI: −22.91 to −5.27 mm2, P = 0.0017). The results from meta-analysis and LD Score Regression provide support for our findings. This investigation unveils the correlations between breast cancer, its various subcategories, and the cerebral cortical structure. Notably, breast cancer of the estrogen receptor-negative variety may elicit more widespread cerebral atrophy.