Immune Microenvironment Heterogeneity in Breast Cancer: Stromal Lymphocytic Patterns Across Molecular and Clinicopathologic Subtypes

Background/Objectives: Tumour-infiltrating lymphocytes (TILs) have emerged as important indicators of tumour–host immune interaction in breast cancer, with increasing prognostic and predictive significance across molecular subtypes. However, most available evidence is derived from Western populations and focuses predominantly on quantitative stromal TIL assessment, while data regarding morphologic stromal immune architecture in Asian populations remain limited. This study evaluated stromal lymphocytic infiltration patterns and their association with molecular and clinicopathologic characteristics in an Indian cohort of invasive ductal carcinoma of the breast. Methods: This retrospective observational pathology-based study included 231 female patients diagnosed with invasive ductal carcinoma at Jawaharlal Nehru Medical College, Aligarh Muslim University, India, between 2009 and 2014. Stromal lymphocytic infiltration was assessed on haematoxylin and eosin-stained sections using a semi-quantitative four-tier scoring system adapted from Guo et al. with whole-section assessment at ×100 magnification by two pathologists. Associations with tumour grade, tumour size, lymph node status, and molecular subtype were assessed using exact and ordinal tests with Holm correction for multiple comparisons. Results: Luminal breast carcinoma was the most common molecular subtype (59.3%), followed by HER2-positive tumours (22.5%) and triple-negative breast cancer (18.2%). Sparse stromal lymphocytic infiltration (score 1) represented the most frequent pattern overall (46.8%). Significant associations were identified between stromal lymphocytic infiltration and molecular subtype, tumour grade, and lymph node status (Holm-adjusted p < 0.001, p = 0.044 and p = 0.044, respectively). Triple-negative and HER2-positive tumours demonstrated higher proportions of moderate-to-dense (score 2–3) infiltration than luminal tumours (40.5% and 48.1% vs. 16.8%). Score 2–3 infiltration was more frequent in Grade III tumours (51.2%) and, conversely, in lymph node-negative than in lymph node-positive tumours (40.8% vs. 21.9%). No statistically significant association was observed between stromal lymphocytic infiltration and tumour size (Holm-adjusted p = 0.071). Conclusions: Stromal lymphocytic infiltration patterns demonstrate substantial heterogeneity across breast cancer molecular subtypes and are associated with molecular subtype and histologic grade, whereas higher infiltration was more frequent in lymph node-negative tumours. These descriptive associations suggest that stromal immune patterns vary with tumour phenotype rather than tumour size. Semi-quantitative morphologic stromal lymphocyte assessment on routine histopathology is inexpensive and feasible in resource-limited settings; its reproducibility and prognostic value require validation.