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Background <p>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.</p> Objective <p>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.</p> Methods <p>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.</p> Results <p>IVW analysis revealed a significant protective effect of ER + BC on MI Complications (<i>P</i> = 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 (<i>P</i> &gt; 0.05) or heterogeneity (<i>P</i> &gt; 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月6日

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  • Zehao Zhao,
  • Binbin Cao,
  • Jiahui Li,
  • Xiaomin Chen

摘要

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.