Abstract 463: Inflammatory breast cancer patients derived explants: Autologous post-mastectomy wound fluid enhances the expression of adhesome and matrisome genes associated with recurrence and metastasis.

Abstract Inflammatory breast cancer (IBC) is an aggressive phenotype, cases diagnosed by IBC is increasing worldwide. Our previous study showed that cytokinome composing wound healing fluid contribute to the aggressive phenotype of inflammatory breast cancer (IBC) by inducing expression of genes associated with extracellular matrix remodelling, recurrence and metastasis. Indeed, studying whether wound drainage fluid, collected after modified radial mastectomy may contribute to IBC recurrence and activation of cancer stem cells is limited by the lack of models. Herein, we hypothesized that post-mastectomy wound fluid (WF) after neoadjuvant chemotherapy (NACT) contains biological mediators that induce recurrence. Methods: Fifty patients (31 non-IBC; 19 IBC) who underwent mastectomy for breast cancer after neoadjuvant chemotherapy were enrolled in the present study. Patient-derived explants (PDEs) were generated from cancer and normal breast tissue of non-IBC and IBC to examine changes in the expression of matricellular- and stemness-related genes after exposing the PDEs to collected autologous postmastectomy-WF for each patient. Results: Gene expression in non-IBC normal primary tissue was significantly different compared to IBC. The IBC cancer tissues showed a significant increase in E-cadherin gene (CDH1) a hall mark of IBC tumor emboli and Matrix metalloproteinases (MMPs). While the proteomic composition of IBC WF was significantly enriched for leptin, PDGF-BB, OSM, angiogenin, IL6, IL8, EGF, and others compared to non-IBC. Autologous IBC WF increased SPARC, MMP2,and MMP3 in normal PDEs, and CDH1, COL6A1, LAMA2, MMP1, MMP3, SELL, and THBS3 in cancer PDEs. We utilized different bioinformatics tools and applications such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) that bridges the gap between biological results and holistic approach to understand the difference between non-IBC and IBC disease biology. Findings provide a robust molecular framework for IBC, identifying candidate biomarkers for recurrence and potential therapeutic targets. The multi-layer validation of expression, interaction, survival, and mutation data strengthens the translational relevance of the detected candidate genes in IBC biology. Citation Format: Mona Mostafa Mohamed, Hossam Taha Mohamed, Alshimaa Tarek, Shrouk Khalaf El-Sayed, Wendy A. Woodward, Jon Mark Hirshon. Inflammatory breast cancer patients derived explants: Autologous post-mastectomy wound fluid enhances the expression of adhesome and matrisome genes associated with recurrence and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 463.