Abstract PS3-13-11: Expression of Brutons tyrosine kinase (BTK) in breast cancer associates with tumor immune microenvironment but lacks predictive value for clinical outcome

Abstract Background: Bruton’s tyrosine kinase (BTK), a downstream mediator of the B-cell receptor (BCR) signaling pathway, is known to be essential in differentiation and proliferation of B-cell. Thus, BTK inhibitors are used to treat refractory mantle cell lymphoma and chronic lymphocytic leukemia. Recent discoveries have revealed the expression of BTK in myeloid-derived suppressor cells, known to worsen breast cancer (BC) outcomes. To this end, it was of interest to investigate the clinical relevance of BTK expression in BC. Methods: Total of 9297 BC patients from 23 independent cohorts with tumor transcriptome and clinical data were analyzed. Results: Based on two independent single-cell sequencing cohorts, approximately 15% of B-cells and 30% of myeloid cells within the tumor microenvironment expressed BTK, while no other cells exhibited BTK expression, suggesting that the BTK expression signal from bulk tumor samples primarily originates from these cells. Correlation with BTK expression was highest in macrophage regulation (r=0.94), and leukocyte fraction, lymphocyte infiltration, TCR Shannon and TCR Richness (all r0.74), but not with BCR Shannon nor BCR Richness. Total macrophage, M1 and M2 macrophage, dendritic cells, total B-cells, memory B-cells, as well as CD8 and CD4 cells were all highly infiltrated in BTK high BCs. Moreover, BTK expression correlated with both PD1 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-11.