Abstract 5131: Breast cancer with insertion or deletion exhibits the immunogenic phenotype

Abstract

Background: Although immunotherapy has been proven to be effective in a wide range of malignant tumors, breast cancer remains to be one of poorly immunogenic tumors and only a small subset of patients with breast cancer achieved benefits from immunotherapy. Therefore, identification of better predictive biomarkers to guide patient selection is highly desirable. It has been reported that insertion or deletion (indels) could create a novel open reading frame and generate more neoantigen which may mediate response to immunotherpay. However, the pattern of indels mutations in breast cancer is still unclear.Methods: Whole-exome sequencing data, RNA-Seq data and clinical data of 1096 breast tumors from The Cancer Genome Altas (TCGA) database were used to analyze the pattern of indels in breast cancer. Next generation sequencing (NGS) data of 81 breast tumors from clinical dataset were also used to validate the indels mutation pattern in different molecular subtype.Results: 81.7% (895/1096) of breast tumors in TCGA dataset harbored at least one indels mutation. Hormonal receptor (HR) negative tumors were associated with higher burden of indels mutations than HR positive tumors in both TCGA dataset (P = 0.05) and NGS-clinical dataset (P = 0.003). Indels were significantly correlated with higher TMB and neoantigen level in TCGA cohort (P < 0.0001). In addition, tumors with at least eight indels mutations (cut off as 80% percentile) exhibited even higher TMB (P < 0.0001) and neoantigen (P < 0.0001) level. Among 45 immune related genes, the mRNA expression of 22 genes were significantly higher in tumors with indels mutations, such as LAG3, IL18, IL6, CTLA4 and PDCD1. Indels group also showed a high levels of genome instability in terms of HRD-LOH (P = 0.004), NtAI (P = 0.000), wGII (P = 0.001) and LST (P =0.014).Conclusions: Breast tumors with indels mutations exhibited the immunogenic phenotype. Further studies are warranted to investigate the potential value of indels as a predictive biomarker for immunotherapy in breast cancer.Note: This abstract was not presented at the meeting.Citation Format: Peng Yuan, Xue Wang, Yuzi Zhang, Jing Zhao, Shangli Cai, Yongmei Yin. Breast cancer with insertion or deletion exhibits the immunogenic phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5131.