ESTRO 2024 - Abstract Book

S5362

Radiobiology - Tumour biology

ESTRO 2024

Results:

Patients were a mix of breast cancer subtypes: ER-positive (n=6), HER2-positive (n=1) and triple-negative (n=3). The two patients who had the best early response to RT on their 2-week MRI scan, had the highest baseline-GLUT1 IHC scores (score=7 and 5.5 vs overall-mean=3.4).

Unsupervised hierarchical clustering was performed to assess gene expression across the cohort (Fig.1). The pre- and post-treatment samples from the same patient clustered together in 6/10 patients (mix of all subtypes). The other four post-treatment samples clustered together (3x ER-positive and 1x triple-negative) suggesting RT was causing co expression of genes across samples and enrichment of radiation-induced pathways. We compared the gene expression pre- and post-RT and identified 198 significantly upregulated genes and 299 significantly downregulated genes (L2Fc≥1/≤-1, adj.p<0.05). Analysis of these differentially expressed genes (DEGs) showed associations with immune/inflammatory response, apoptosis, cell cycle, DDR and cellular response to stress. GSEA identified enriched pathways including cell cycle, eosinophil chemotaxis, JAK-STAT, chemokine and NOD-like receptor signalling pathways, suggesting activation of radiation-induced immune response and cell death pathways. Further analysis of the immune and stromal cell populations through bulk RNA-seq using the Xcell-tool 3 demonstrated a significant increase in both immune and stromal-cell populations post-RT, in particular fibroblasts and dendritic cells.