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

Authors

Valeria Zuccalà, Nicoletta Staropoli, Caterina Labanca, Gabriele Ricciardi, Pietro Tralongo, Vincenzo Fiorentino, Elisabetta Procopio, Maria Renne, Antonio Ieni, Maurizio Martini, Pierfrancesco Tassone, Pierosandro Tagliaferri

Published in

Diseases (Basel, Switzerland). Volume 14. Issue 10. Oct 03, 2026. Epub Oct 03, 2026.

Abstract

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.

PMID:
42929994
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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