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Abstract 4011: Prognostic value of transcriptomic analysis in residual post neo-adjuvant triple negative breast cancer tumors


 Background: Triple negative breast cancer is the most aggressive type of breast cancer. Approximately 50% of TNBC patients respond to pre-operative neo-adjuvant chemotherapy (NAC), however those patients with residual disease (non-pathological complete response or non-pCR) have a very poor prognosis. Recently, the use of capecitabine in the adjuvant setting was shown to increase disease-free survival in non-pCR patients. However, there are no biomarkers to identify patients who may benefit from adjuvant capecitabine. Moreover, novel therapeutic targets are needed to treat patients with non-pCR.
 Methods: RNA extracted from 32 Formalin Fixed Paraffin Embedded (FFPE) residual post-NAC tumor samples underwent NanoString nCounter gene expression analysis using the BC360 panel as well as RNAseq.
 Results: Comparison of tumors from poor (RFS<2 yrs) and good prognosis (RFS>2 yrs) patients showed 65 genes differentially expressed (≥1.5 fold change and p<0.05) by nCounter. 40 of these genes had differential expression also validated by RNAseq (R2= 0.96) and were selected for further pathway analysis. Gene Set Enrichment Analysis (GSEA) showed an enrichment for biological pathways involved in cell cycle, with all genes in this set upregulated in the poor prognosis group. GSEA analysis of 310 upregulated genes identified by RNAseq showed an enrichment for biological pathways associated with cell population proliferation and skin development. Interestingly, one of the upregulated genes identified was TYMS, encoding thymidylate synthase, the target of capecitabine, which showed 2-fold increased expression in the poor prognosis group (p≤0.005).
 Conclusion: Our results suggest that residual tumors from TNBC patients who relapse within two years of surgery show transcriptomic evidence of increased proliferation and that expression levels of TYMS may be a potential biomarker to select patients for capecitabine in the adjuvant setting.
 Citation Format: Adriana Aguilar-Mahecha, Yasamin Majedi, Oluwadara Elebute, Josiane Lafleur, Andreas Papadakis, Cathy Lan, Manuela Pelmus, Touhidur Rashid, Sarah Jenna, Mark Basik. Prognostic value of transcriptomic analysis in residual post neo-adjuvant triple negative breast cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4011.