Immune- and Stromal-Associated Tissue-Context Profiles in Pretreatment Triple-Negative Breast Cancer: An Exploratory...

We examined combinations of immune- and stromal-associated features in pretreatment triple-negative breast cancer (TNBC) biopsies and explored their clinical and germline associations.

This retrospective study included 24 women with nonmetastatic TNBC from a clinically selected BRCA1/BRCA2-tested cohort. Two pathologists, blinded to clinical and germline data, jointly assessed stromal tumor-infiltrating lymphocytes (sTILs), programmed death-ligand 1 (PD-L1), CD68/CD163-positive macrophages, and CD117/tryptase-positive mast cells. Profiles were assigned before unblinding. A second blinded joint sTIL assessment provided continuous estimates for subsequent hierarchical clustering; profile assignments remained unchanged.

Profiles I-III comprised seven, 13, and four tumors, respectively. Profile I combined higher sTILs and PD-L1 with a CD68-high/CD163-low pattern and rare mast cells. Profile II showed lower sTILs and PD-L1, a CD68-low/CD163-high pattern, and dense mast-cell hotspots; Profile III had minimal sTILs, low macrophage counts, and no mast cells detected in evaluated fields. Clustering reproduced these assignments. All four patients with pathogenic/likely pathogenic germline BRCA1/BRCA2 variants were in Profile I (adjusted p = 0.030); omitting one positive case at a time increased the adjusted p value to 0.068. Seven of 16 neoadjuvant-treated patients achieved pathologic complete response. Five posttreatment recurrences and seven deaths were recorded; exploratory comparisons of pathologic complete response and overall survival were inconclusive.

These profiles describe different combinations of lymphocytic infiltration, PD-L1 expression, macrophage counts, and mast-cell hotspots. The profiles and the exploratory BRCA1/BRCA2 finding require validation in larger, independent cohorts before clinical use.