International journal of women's health · 2026
Association of Body Mass Index with Tumor-Infiltrating Lymphocytes and Treatment Response in Early HER2-Positive Breast Cancer.
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Sánchez Gómez Rosa, Pérez-Míes Belén, Palacios José, Moreno Bueno Gema, Calvo Isabel, Solorzano José L, Neria Fernando, Fernandez-Abad María, González-Martínez Silvia, García-Estevez Laura
Аннотация
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.
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.