Predictive Value of TILs and SLC35A2 Expression in Tumor Microenvironment for Neoadjuvant Therapy Response in Breast Cancer

Xinhua LI; Kejiao WU; Jiamin WU

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Xinhua LI, Kejiao WU, Jiamin WU. Predictive Value of TILs and SLC35A2 Expression in Tumor Microenvironment for Neoadjuvant Therapy Response in Breast Cancer[J]. Journal of Kunming Medical University.

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Xinhua LI, Kejiao WU, Jiamin WU. Predictive Value of TILs and SLC35A2 Expression in Tumor Microenvironment for Neoadjuvant Therapy Response in Breast Cancer[J]. Journal of Kunming Medical University.

Xinhua LI, Kejiao WU, Jiamin WU. Predictive Value of TILs and SLC35A2 Expression in Tumor Microenvironment for Neoadjuvant Therapy Response in Breast Cancer[J]. Journal of Kunming Medical University.

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Predictive Value of TILs and SLC35A2 Expression in Tumor Microenvironment for Neoadjuvant Therapy Response in Breast Cancer

Department of Pathology，Nanping First Hospital Affiliated to Fujian Medical University，Nanping Fujian 353000，China

Received Date: 2026-01-09

Abstract

Abstract

Objective To investigate the differences in tumor-infiltrating lymphocytes （TILs） and solute carrier family 35 member A2 （SLC35A2） expression in the tumor microenvironment across different molecular subtypes of breast cancer and their predictive value for neoadjuvant therapy （NAT） response. Methods A prospective study was conducted on 202 breast cancer patients scheduled for NAT admitted to the First Affiliated Hospital of Nanping, Fujian Medical University from February 2022 to May 2024. The cohort consisted of 13 cases of Luminal A subtype, 108 cases of Luminal B subtype, 39 cases of human epidermal growth factor receptor 2 （HER-2） overexpression subtype, and 42 cases of triple-negative breast cancer （TNBC）. According to the NAT response, patients were stratified into the pathological complete response （pCR） group （n = 78） and non-pCR group （n = 124）. Differences in tumor microenvironment TILs and SLC35A2 expression were compared across different molecular subtypes and NAT response status. Multivariate logistic regression analysis was performed to identify factors influencing NAT response. The predictive value of TILs and SLC35A2 for NAT response was analyzed using both the AND rule （simultaneous high expression of both TILs and SLC35A2） and the OR rule （high expression of either TILs or SLC35A2）. Results Among different molecular subtypes, high expression rates of TILs in HER-2 overexpression （61.54%） and TNBC （57.14%） were significantly higher than those in Luminal B （24.07%） and Luminal A （23.08%） subtypes （P < 0.05）. The high expression rate of SLC35A2 in Luminal A （69.23%） was significantly higher than in TNBC （23.81%, P < 0.05）. Compared to the pCR group, the non-pCR group showed significant differences in high expression rates of TILs（17.74% vs. 70.51%）, high expression rate of SLC35A2 （49.19% vs. 21.79%）, molecular subtype, treatment regimen, T stage and lymph node metastasis （all P < 0.05）. After adjusting for confounding factors by multivariate logistic regression analysis, high TILs expression was an independent protective factor for NAT response （OR = 0.589, 95% CI: 0.467～0.744, P < 0.001）, while high SLC35A2 expression was an independent risk factor （OR = 2.737, 95% CI: 1.651～4.539, P < 0.001）. Predictive value analysis demonstrated that the OR rule （high expression of either marker） achieved a sensitivity of 92.74% （95% CI: 85.21～97.18）, significantly higher than TILs alone （82.26%, adjusted P = 0.0013） and SLC35A2 alone （49.19%, adjusted P < 0.0001）. The accuracy was 83.66% （95% CI: 77.98～88.34）, significantly higher than TILs alone （77.72%, adjusted P = 0.014） and SLC35A2 alone （60.40%, adjusted P < 0.0001）. The AND rule （simultaneous high expression of both） achieved a specificity of 96.15% （95% CI: 90.87～98.76）, significantly higher than TILs alone （70.51%） and SLC35A2 alone （78.21%）（adjusted P < 0.0001 for both）. Conclusion TILs and SLC35A2 expression demonstrates significant differences across different molecular subtypes of breast cancer. High TILs expression is associated with superior NAT response, whereas high SLC35A2 expression predicts poor NAT response. The OR rule （high expression of either marker） enhances the predictive value for NAT response and provides valuable reference for clinical identification of patients who may benefit from NAT.
- Breast cancer,
- Molecular subtypes,
- Tumor-infiltrating lymphocytes,
- Solute carrier family 35 member A2,
- Response to neoadjuvant therapy

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