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/m 2 . Patients with BMI ≥ 25 kg/m 2 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. Keywords: body mass index, human epidermal growth factor receptor 2-positive breast cancer, obesity, treatment response, tumor-infiltrating lymphocytes
Gómez et al. (Fri,) studied this question.