Immune- and Stromal-Associated Tissue-Context Profiles in Pretreatment Triple-Negative Breast Cancer: An Exploratory Institutional Cohort Study.
6 affiliations
- 1Division of Pathology, Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", University of Messina, 98125 Messina, Italy.
- 2Medical Oncology Unit, "R. Dulbecco" Teaching Hospital (Mater Domini Facility), Magna Græcia University and Cancer Center, Campus Salvatore Venuta, 88100 Catanzaro, Italy.
- 3Department of Experimental and Clinical Medicine, Magna Græcia University, Campus Salvatore Venuta, 88100 Catanzaro, Italy.
- 4Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98125 Messina, Italy.
- 5Pathology Unit, "Renato Dulbecco" Hospital, 88100 Catanzaro, Italy.
- 6Surgery Unit, "R. Dulbecco" Teaching Hospital (Mater Domini Facility), Magna Græcia University and Cancer Center, Campus Salvatore Venuta, 88100 Catanzaro, Italy.
Abstract
Background/objectives
We examined combinations of immune- and stromal-associated features in pretreatment triple-negative breast cancer (TNBC) biopsies and explored their clinical and germline associations.Methods
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.Results
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.Conclusions
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.
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BibTeX
@article{zuccala2026immune,
title = {{Immune- and Stromal-Associated Tissue-Context Profiles in Pretreatment Triple-Negative Breast Cancer: An Exploratory Institutional Cohort Study.}},
author = {Valeria Zuccalà and Nicoletta Staropoli and Caterina Labanca and Gabriele Ricciardi and Pietro Tralongo and Vincenzo Fiorentino and Elisabetta Procopio and Maria Renne and Antonio Ieni and Maurizio Martini and Pierfrancesco Tassone and Pierosandro Tagliaferri},
journal = {Diseases (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/diseases14100367},
url = {https://europepmc.org/article/MED/42929994},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immune- and Stromal-Associated Tissue-Context Profiles in Pretreatment Triple-Negative Breast Cancer: An Exploratory Institutional Cohort Study.
AU - Valeria Zuccalà
AU - Nicoletta Staropoli
AU - Caterina Labanca
AU - Gabriele Ricciardi
AU - Pietro Tralongo
AU - Vincenzo Fiorentino
AU - Elisabetta Procopio
AU - Maria Renne
AU - Antonio Ieni
AU - Maurizio Martini
AU - Pierfrancesco Tassone
AU - Pierosandro Tagliaferri
PY - 2026
DA - 2026/10/03
JO - Diseases (Basel, Switzerland)
DO - 10.3390/diseases14100367
UR - https://europepmc.org/article/MED/42929994
AB - Background/objectives We examined combinations of immune- and stromal-associated features in pretreatment triple-negative breast cancer (TNBC) biopsies and explored their clinical and germline associations.Methods 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.Results 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.Conclusions 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.
SN - 2079-9721
ER -