The Impact of Sleep on Breast Cancer-Specific Mortality: A Mendelian Randomisation Study

Background: The relationship between sleep traits and survival in breast cancer is uncertain and complex. There are multiple biological, psychological and treatment-related factors that could link sleep and cancer outcomes. Previous studies could be biased due to methodological limitations such as reverse causation and confounding. Here, we used two-sample mendelian randomisation (MR) to investigate the causal relationship between sleep and breast cancer mortality. Methods: Publicly available genetic summary data from females of European ancestry from UK Biobank and 23andme and the Breast Cancer Association Consortium were used to generate instrumental variables for sleep traits (chronotype, insomnia symptoms, sleep duration, napping, daytime-sleepiness, and ease of getting up (N= 446,118-1,409,137)) and breast cancer outcomes (15 years post-diagnosis, stratified by tumour subtype and treatment (N=91,686 and Ndeaths=7,531 over a median follow-up of 8.1 years)). Sensitivity analyses were used to assess the robustness of analyses to MR assumptions. Results: Initial results found some evidence for a per category increase in daytime-sleepiness reducing overall breast cancer mortality (HR=0.34, 95% CI=0.14, 0.80), and for insomnia symptoms reducing odds of mortality in oestrogen receptor positive breast cancers not receiving chemotherapy (HR=0.18, 95% CI=0.05, 0.68) and in patients receiving aromatase inhibitors (HR=0.23, 95% CI=0.07, 0.78). Importantly, these relationships were not robust following sensitivity analyses meaning we could not demonstrate any causal relationships. Conclusions: This study did not provide evidence that sleep traits have a causal role in breast cancer mortality. Further work characterising disruption to normal sleep behaviours and its effects on tumour biology, treatment compliance and quality of life are needed.