Abstract P5-03-06: Effect of Sleep Traits on Subtype Specific Breast Cancer Survival: a Mendelian Randomization Analysis

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Abstract Background There is increasing interest in the relationship between sleep traits and both quality of life and survival in breast cancer. Recent work has found that oestrogen receptor positive (ER+) tumour cells are more likely to spread, via the circulation, at night than in the morning, providing support for a potential role of sleep characteristics influencing metastasis and therefore survival from breast cancer. The aim of this study was to investigate causal effects of sleep traits on subtype-specific breast cancer survival. Methods Single-nucleotide polymorphisms (SNPs) identified from GWAS associated with sleep traits with were used as a genetic instruments for Chronotype (N=697,828), Insomnia (N=1,331,010), Sleep Duration (N=446,118), Napping (N=452,633), Daytime sleepiness(N=452,071) and Ease of Getting up (N=461,658). All instruments were identified in data from UK Biobank, except chronotype and insomnia, which were identified in meta-analyses of UK Biobank and 23andme. For all instruments female-specific effect estimates were used. For these SNPs, summary statistics of their association with breast cancer survival were obtained from GWAS meta-analyses of European women from the Breast Cancer Association Consortium (BCAC), (N=91,686, with 7531 breast cancer specific deaths over a median follow-up of 8.1 years). To estimate the causal effect of the sleep traits on breast cancer survival, we applied two-sample MR for both overall and subtype-specific breast cancer (Luminal A-like, Luminal B-like, Human Epidermal Growth Factor 2 (Her2) positive, Her2 negative and triple negative (TNBC)). Further stratification by tumour characteristics at diagnosis and treatment received was also used. Sensitivity analyses were used to assess the robustness of main analyses to MR assumptions. Results For every hour increase in sleep duration, we observed worsening 5-year breast cancer specific survival in patients with ER+ tumours who received endocrine therapy (HR: 2.55, 95% CI: 1.10, 5,82) and for all patients receiving aromatase inhibitors (HR: 9.57, 95% CI: 1.61, 57.10). Conversely, improved 5-year survival was observed in patients with ER- tumours who received chemotherapy (HR: 0.30, 95% CI: 0.10, 0.87) and all patients receiving taxanes (HR: 0.23, 95% CI: 0.05, 0.98). We also observed that an increase in daytime sleepiness improved 15-year survival in patients both overall (HR: 0.34, 95% CI: 0.14, 0.80) and with lymph node negative tumours at diagnosis (HR: 0.12, 95% CI: 0.02, 0.64). Detailed sensitivity analyses are ongoing. Conclusions The current study uses a causal approach to identify potential effects between sleep patterns and breast cancer survival and confirms the previously observed relationships with increased sleep duration and worse survival in ER+ breast cancer. The reasons for opposite effects seen in those with ER- and those receiving taxanes needs further mechanistic work. Although the improved survival in relation to increased daytime sleepiness appears to be in-keeping with previous findings, this may largely reflect shorter sleep duration. Further work accurately characterising sleep quality, rather than duration in those with breast cancer, examining the effects on quality of life and survival and establishing mechanisms are needed. Citation Format: Bryony Hayes, Richard Martin, Deborah Lawlor, Rebecca Richmond, Tim Robinson. Effect of Sleep Traits on Subtype Specific Breast Cancer Survival: a Mendelian Randomization Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-06.