Abstract 47P
Background
Triple-negative breast cancer (TNBC) is a highly aggressive subtype primarily managed with chemotherapy, as immune therapy often exhibits limited success. The Indian population presents a distinctive scenario, characterized by a higher proportion of younger patients with aggressive breast cancer (BC), particularly TNBC, which is associated with a poor prognosis. Understanding the tumor microenvironment (TME) is important to plan better treatment strategies.
Methods
We employed Digital Spatial Profiling (DSP) to evaluate 5 younger (age < 50) and 6 older (age ≥ 50) TNBC patients. DSP was performed according to the nanoString GeoMX standard protocol for cancer transcriptomics atlas (CTA) panels. Tissue microarray was constructed using Quick Ray. Morphology marker staining was carried out using the Solid Tumor morphology kit. Subsequently, regions of interest (ROIs) were selected based on morphologic markers and stained H&E slides. Following this, Areas of Illumination (AOIs) were chosen based on PanCK staining to delineate tumor and non-tumor compartments. Data were normalized and subjected to differential expression (DEGs) and pathway analysis using the GeoMX CTA panel.
Results
Analysis showed distinct spatial expression patterns in younger and older patients. In the tumor compartment, we identified 158 DEGs (up=75, down=83), while the non-tumor compartment exhibited 79 DEGs (up=25, down=54) in younger patients. Key pathways such as Cancer Antigens, T cell Checkpoints, Cytotoxicity, B-cells, and T cells were downregulated in the tumor compartment, whereas pathways like TCR, Notch, Wnt, and Immortality-Stemness were upregulated. In the non-tumor compartment, pathways like EMT, HIF1 Signaling, TH9 Differentiation, and Endocytosis were upregulated. These findings were validated in the TCGA cohort with both younger and older patients.
Conclusions
The study highlights age-related disparities in the TME and aggressive phenotypes in TNBC, identifying enriched pathways in both tumor and non-tumor compartments. In vivo experimental validation is essential to translate these findings into potential therapeutic strategies for younger BC patients.
Legal entity responsible for the study
St. John's Research Institute.
Funding
DBT/ WellcomeTrust India Alliance Fellowship/Grant [IA/CPHI/18/1/503938].
Disclosure
All authors have declared no conflicts of interest.