Association of Body Mass Index with Tumor-Infiltrating Lymphocytes and Treatment Response in Early HER2-Positive Breast Cancer.

BACKGROUND

Immune-related biomarkers such as stromal tumor-infiltrating lymphocytes (TILs) are associated with response to neoadjuvant therapy in HER2+ breast cancer. Host-related factors, including BMI, may influence the tumor immune microenvironment and modify the predictive value of immune infiltration.

METHODS

In this retrospective cohort study, we evaluated associations between BMI, stromal TIL density, selected immune checkpoint markers (PD-1 and TIM-3), leptin receptor (Ob-R) expression, and pathological complete response (pCR) in patients with early-stage HER2+ breast cancer treated with neoadjuvant HER2-targeted therapy.

RESULTS

Of 101 patients analyzed, 48.0% had a BMI ≥25 kg/m2. Patients with BMI ≥25 kg/m2 exhibited higher stromal TIL density (p = 0.011), higher frequency of PD-1 positivity (p = 0.058), and higher Ob-R expression (p = 0.043). BMI was not directly associated with pCR. In multivariable analysis, hormone receptor positivity was inversely associated with pCR (odds ratio [OR] = 0.15; 95% confidence interval [CI], 0.04-0.51; p = 0.004), whereas higher stromal TIL density was independently associated with increased odds of pCR (OR = 1.37; 95% CI, 1.03-1.93; p = 0.048). A significant interaction observed between BMI and stromal TIL density (interaction OR = 0.99; 95% CI, 0.97-1.00; p = 0.044) indicated that the association between immune infiltration and treatment response differed according to BMI. In early-stage HER2+ breast cancer, stromal TIL density and PD-1 expression are associated with response to neoadjuvant therapy, while BMI appears to modify the relationship between immune infiltration and pCR.

CONCLUSION

Host-related factors, as captured by BMI, may influence the tumor immune microenvironment and predictive value of immune biomarkers in early-stage HER2-positive breast cancer. As the study was exploratory, these observations warrant further study.