PS4-05-11: Breast Cancer Drives Detectable Reprogramming in White Blood Cells and Platelets

Abstract Background: Tumour-induced immune reprogramming is a key mechanism by which cancers can evade immune surveillance and promote disease progression. In recent in vitro studies, we demonstrated that triple-negative breast cancer (TNBC) cells can modify gene expression in THP1 monocytes, through phenotypic and transcriptomic changes consistent with immune dysfunction. These effects included activation of oncogenic signalling pathways, upregulation of IL6, and enhancement of proliferative signals. Here we report on molecular changes in white blood cells and platelets in women with breast cancer. Methods: Blood samples were collected from participants in the IDBC clinical study (clinicaltrials.gov/study/NCT04495244) prior to biopsy. Samples were fractionated into white blood cells (WBCs) and platelets. RNA was extracted, transcriptomic analysis with RNA sequencing performed, and expression profiles compared between cancer and non-cancer samples. These samples were also compared to those from a model system of THP1 monocytes co-cultured with MDA-MB-231 TNBC cells that was used to identify key regulatory genes. Differential gene expression and pathway analyses were conducted using Ingenuity Pathway Analysis (IPA). Results: For clinical samples, 11,355 differentially expressed genes (DEGs) were identified between cancer and non-cancer: 1,741 were unique to the cancer WBC fraction and 2,070 were unique to the cancer platelet fraction. Key shared upstream regulators between clinical WBCs and platelets and in vitro model THP1 included TRAF2, ZNF281, BMP4, SMAD3, and ITGA11 (WBCs), as well as IFNG, STING1, CDK6, RIPK2, CD44, TGM2, and STAT1 (platelets). In WBCs, the upstream regulators point to a transcriptional landscape shaped by TGF-β signaling, cellular stress response, and integrin-mediated remodeling, consistent with immune tolerance and altered cell trafficking. In contrast, platelet-derived signatures were enriched for IFNG, STING1 and related factors, suggesting a shift toward innate immune sensing, inflammatory signaling, cell cycle activity and adhesion dynamics. Conclusions: WBCs and platelets exhibited differential expression of key immune-related transcripts in cancer versus non-cancer clinical samples, and were in alignment with tumor-induced changes in a in vitro co-culture model. These results demonstrate the presence of tumour-induced blood reprogramming that is detectable in blood, with WBCs reflecting chronic signaling modulation and platelets demonstrating acute immune activation and vascular interaction. This supports the biological basis for using tumor-educated immune changes as a foundation for enabling early detection and therapeutic strategies. Citation Format: O. A. KHARENKO, K. Norek, J. Kennard, K. Fuh, R. D. Shepherd, K. D. Rinker.Breast Cancer Drives Detectable Reprogramming in White Blood Cells and Platelets [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-05-11.