Systemic inflammation and immune status play critical roles in carcinogenesis. However, evidence regarding the association between the lymphocyte-to-monocyte ratio (LMR) and the risk of breast cancer (BC) remains limited.This study aims to investigate the relationship between LMR and BC risk.

A total of 13 519 participants with complete LMR and BC data were identified from the U.S. National Health and Nutrition Examination Survey (NHANES) 2005—2018. Multivariable weighted logistic regression models, restricted cubic spline analyses, and subgroup analyses were conducted to evaluate the independent association between LMR and BC risk. Sensitivity analyses were performed to assess the robustness of the findings.

A significant U-shaped association was observed between LMR and BC risk, with an inflection point at 1.82. When LMR was ≤1.82, it was inversely associated with BC risk, with each one-unit increase in LMR corresponding to a 76% reduction in BC risk (OR=0.24, 95% CI: 0.18-0.31). Above this threshold, the association was no longer statistically significant. In the LMR quartile groups, the highest quartile (Q4) showed a significant reduction in breast cancer risk of approximately 47% compared to the Q1 group (OR=0.53, 95% CI: 0.38-0.74). Likelihood ratio tests indicated that the piecewise linear model provided a better fit than the linear model. Subgroup and interaction analyses revealed significant differences in the association between LMR and BC risk between participants with and without diabetes.

This study is the first to demonstrate a non-linear (broad U-shaped) association between LMR and BC risk,indicating that both low and high LMR levels are associated with an increased risk of BC. Maintaining LMR within a stable range may help prevent and slow the development and progression of breast cancer. Further large-scale prospective cohort studies are warranted to validate these findings.