Association Between Peripheral Blood Lymphocyte Count and HER2 Status in Breast Cancer: A Retrospective Study

Background: Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is associated with aggressive tumor biology and a distinct immune microenvironment. Although the absolute lymphocyte count (ALC) in peripheral blood is widely used as a routine indicator of systemic immune function, its relationship with HER2 status remains insufficiently explored. Methods: This retrospective study investigated the association between pretreatment peripheral ALC and HER2 status in a cohort of breast cancer patients. Multivariate logistic regression, random forest modeling, and restricted cubic spline (RCS) analyses were employed to assess this relationship. Subgroup analyses were conducted across major clinical and pathological variables to evaluate their robustness. In parallel, tumor immune infiltration profiles were analyzed using the TIMER 2.0 platform. Results: A robust and consistent inverse association was observed between ALC and HER2-positive status across all analytical approaches. In fully adjusted logistic regression models, higher ALC was independently associated with lower odds of HER2 positivity (OR= 0.53, 95% CI: 0.37-0.77, P