Tumor-Infiltrating Lymphocyte Level Consistently Correlates with Lower Stiffness Measured by Shear-Wave Elastography: Subtype-Specific Analysis of Its Implication in Breast Cancer

Abstract

Simple Summary Tumor stiffness in breast cancer displays varied clinical implications depending on the tumor subtype, with higher stiffness indicating a more aggressive tumor biology particularly in hormone receptor-positive and HER2-negative breast cancer. This study investigated the relationship between tumor stiffness, measured by shear-wave elastography, and clinicopathologic parameters such as the tumor-infiltrating lymphocytes (TIL) levels in 803 breast cancer patients across different subtypes. The results showed that higher tumor stiffness is associated with more aggressive tumor features, especially in hormone receptor-positive and HER2-negative breast cancer. Across all subtypes, a positive correlation was observed between tumor stiffness and size, while the TIL level showed a significant negative correlation. The TIL level was the only parameter to correlate with low tumor stiffness consistently and significantly, which was further confirmed by linear regression.Abstract Background: We aimed to elucidate the clinical significance of tumor stiffness across breast cancer subtypes and establish its correlation with the tumor-infiltrating lymphocyte (TIL) levels using shear-wave elastography (SWE). Methods: SWE was used to measure tumor stiffness in breast cancer patients from January 2016 to August 2020. The association of tumor stiffness and clinicopathologic parameters, including the TIL levels, was analyzed in three breast cancer subtypes. Results: A total of 803 patients were evaluated. Maximal elasticity (Emax) showed a consistent positive association with an invasive size and the pT stage in all cases, while it negatively correlated with the TIL level. A subgroup-specific analysis revealed that the already known parameters for high stiffness (lymphovascular invasion, lymph node metastasis, Ki67 levels) were significant only in hormone receptor-positive and HER2-negative breast cancer (HR + HER2-BC). In the multivariate logistic regression, an invasive size and low TIL levels were significantly associated with Emax in HR + HER2-BC and HER2 + BC. In triple-negative breast cancer, only TIL levels were significantly associated with low Emax. Linear regression confirmed a consistent negative correlation between TIL and Emax in all subtypes. Conclusions: Breast cancer stiffness presents varying clinical implications dependent on the tumor subtype. Elevated stiffness indicates a more aggressive tumor biology in HR + HER2-BC, but is less significant in other subtypes. High TIL levels consistently correlate with lower tumor stiffness across all subtypes.