Is ER-positive breast cancer a shield against myocardial infarction and its complications? A Mendelian randomization approach

BACKGROUND: Estrogen receptor-positive breast cancer (ER + BC) is the most prevalent subtype of breast cancer. However, the causal relationship between ER + BC and myocardial infarction complications remains unclear. While observational studies suggest a potential association between ER + BC and cardiovascular events, existing evidence does not provide sufficient causal inference. Mendelian randomization (MR) serves as a powerful method for investigating the causal links between genetic variables and disease outcomes. OBJECTIVE: The central goal of this study is to assess the genetic basis for the associations between ER + BC and complications of myocardial infarction (MI Complications), as well as between ER + BC and acute myocardial infarction (Acute MI), employing MR as the analytical framework. METHODS: A two-sample MR analysis was conducted, with ER + BC as the exposure variable and Acute MI and MI Complications as outcomes.The exposure and outcome data in this study were both downloaded from publicly available databases on MR-Base, a resource provided by the MRC Integrative Epidemiology Unit.Causal inference was performed using inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. Heterogeneity was assessed with Cochrane's Q test, and pleiotropy was evaluated using the MR-Egger intercept test and MR-PRESSO, to provide additional assurance regarding the robustness of the findings. RESULTS: IVW analysis revealed a significant protective effect of ER + BC on MI Complications (P = 0.018), with a P-value of 0.007 for the effect on Acute MI. However, MR-Egger suggests that the relationship between ER + BC and Acute MI exhibits pleiotropy.Additionally, the MR analysis found no evidence of pleiotropy (P > 0.05) or heterogeneity (P > 0.05) between ER + BC and MI Complication, suggesting that the causal relationship is not confounded by other potential factors. Furthermore, the leave-one-out sensitivity analysis confirmed the stability of the findings. CONCLUSION: This study provides genetic evidence supporting a protective relationship of causality between ER + BC and Acute MI, as well as MI Complications. The MR analysis suggests that ER + BC may reduce the risk of MI Complications. These findings offer new perspectives for clinical interventions and public health policies.