Prevalence of Stromal Tumor Infiltrating Lymphocytes in Invasive Breast Carcinoma

Background: Tumor-infiltrating lymphocytes (TILs) represent the host immune response within the breast cancer microenvironment and are increasingly recognized as histopathological biomarkers with potential prognostic and predictive significance. However, their distribution across molecular subtypes and disease stages in routine diagnostic practice remains incompletely characterized, particularly in pathology-based cohorts. Aim: To assess the prevalence of stromal TILs in invasive breast carcinoma and evaluate their association with molecular subtypes and pathological stage.Methods: This prospective study included 70 patients with invasive breast carcinoma. Molecular subtyping was performed using immunohistochemistry for estrogen receptor, progesterone receptor, HER2, and Ki-67, with fluorescence in situ hybridization for HER2-equivocal cases. Stromal TILs were evaluated on hematoxylin and eosin–stained sections according to International TILs Working Group recommendations and recorded as the percentage of stromal area occupied by mononuclear inflammatory cells. TILs were categorized as low (0–10%), intermediate (11–59%), or high (≥60%). Associations between TIL levels, molecular subtype, and stage were analyzed using chi-square or Fisher's exact tests.Results: The overall mean stromal TIL score was 31.3% (median 10%). Luminal HER2-negative low Ki-67 tumors demonstrated the lowest infiltration (mean 19.3%; 81% low TILs). Luminal HER2-negative high Ki-67 tumors showed relatively higher immune activity (mean 40.4%; 54% intermediate/high). HER2-positive tumors exhibited predominantly low-to-intermediate infiltration, while triple-negative breast cancers showed the greatest heterogeneity. Among early-stage cases, 63% had low TILs, whereas advanced-stage tumors showed only low-to-intermediate levels. No statistically significant associations were observed.Conclusion: Stromal TIL distribution varies by molecular subtype, with greater immune activity in proliferative luminal, HER2-positive, and triple-negative tumors. Routine histopathological assessment of TILs offers a simple, reproducible, and cost-effective approach for evaluating tumor–immune interaction and may support prognostication and therapeutic stratification.

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Journal
Annals of Pathology and Laboratory Medicine
Published
2026-04-06
DOI
https://doi.org/10.21276/apalm.3801
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
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article

Prevalence of Stromal Tumor Infiltrating Lymphocytes in Invasive Breast Carcinoma

Narendra Hulikal, Alekhya Maduri, Rukmangadha Nandyala, T. C. Kalawat et al.
Annals of Pathology and Laboratory Medicine
Cancer Immunotherapy and Biomarkers
article

Prevalence of Stromal Tumor Infiltrating Lymphocytes in Invasive Breast Carcinoma

Narendra Hulikal, Alekhya Maduri, Rukmangadha Nandyala, T. C. Kalawat, A. Durga Maha Lakshmi
article en

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) represent the host immune response within the breast cancer microenvironment and are increasingly recognized as histopathological biomarkers with potential prognostic and predictive significance. However, their distribution across molecular subtypes and disease stages in routine diagnostic practice remains incompletely characterized, particularly in pathology-based cohorts. Aim: To assess the prevalence of stromal TILs in invasive breast carcinoma and evaluate their association with molecular subtypes and pathological stage.Methods: This prospective study included 70 patients with invasive breast carcinoma. Molecular subtyping was performed using immunohistochemistry for estrogen receptor, progesterone receptor, HER2, and Ki-67, with fluorescence in situ hybridization for HER2-equivocal cases. Stromal TILs were evaluated on hematoxylin and eosin–stained sections according to International TILs Working Group recommendations and recorded as the percentage of stromal area occupied by mononuclear inflammatory cells. TILs were categorized as low (0–10%), intermediate (11–59%), or high (≥60%). Associations between TIL levels, molecular subtype, and stage were analyzed using chi-square or Fisher's exact tests.Results: The overall mean stromal TIL score was 31.3% (median 10%). Luminal HER2-negative low Ki-67 tumors demonstrated the lowest infiltration (mean 19.3%; 81% low TILs). Luminal HER2-negative high Ki-67 tumors showed relatively higher immune activity (mean 40.4%; 54% intermediate/high). HER2-positive tumors exhibited predominantly low-to-intermediate infiltration, while triple-negative breast cancers showed the greatest heterogeneity. Among early-stage cases, 63% had low TILs, whereas advanced-stage tumors showed only low-to-intermediate levels. No statistically significant associations were observed.Conclusion: Stromal TIL distribution varies by molecular subtype, with greater immune activity in proliferative luminal, HER2-positive, and triple-negative tumors. Routine histopathological assessment of TILs offers a simple, reproducible, and cost-effective approach for evaluating tumor–immune interaction and may support prognostication and therapeutic stratification.

Annals of Pathology and Laboratory MedicineVol. 13(4)
Sri Venkateswara Institute of Medical Sciences (IN)
Partnerships for the goals
Openalex Percentile: Top 8%
Cancer Immunotherapy and Biomarkers
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