Abstract 1705: Identification of an immune gene expression signature for progression of breast ductal carcinoma in situ (dcis)

Abstract

Abstract Introduction. DCIS is a potential precursor of invasive breast cancer (IBC). Immune escape might play a critical role in the transition from DCIS to IBC. We aim to identify an immune-related gene expression signature of DCIS to distinguish hazardous lesions, and to avoid the burden of overtreatment in women with less harmful DCIS. Since tumor-infiltrating lymphocytes (TILs) occur more frequently in hormone receptor-negative, Her-2 positive DCIS, we focused the analysis on this subtype. Methods. We performed a prospective nested case-control study involving women with pure DCIS (hormone receptor-negative, Her-2 positive, TILs ≥ 20%), treated with breast conservative surgery with or without radiotherapy. Cases were defined as women with DCIS developing subsequent ipsilateral breast event (IBE), controls as women with DCIS without IBE at 8 years of follow-up. Next-generation sequencing gene expression assay (Oncomine™ Immune Response Research Assay) targeting 395 genes associated with tumor-immune systems interactions was performed on RNA extracted from DCIS samples of 25 cases and 25 age- and radiotherapy-matched controls. In order to obtain reliable results, we considered adequate samples with mapped reads > 1 million and valid reads > 800.000. Normalized gene-level count data generated from the run were further processed with Affymetrix™. A Volcano plot was also employed in order to distinguish genes differently expressed between cases and controls according to the log-gene-level fold change and the ANOVA test (p values < 0.05). Univariate (Log-rank) and multivariate Cox proportional hazard models identified genes associated with the disease free survival. Results. Thirty-one samples (15 cases; 16 controls) reached the quality parameters. The analysis identified 11 genes with a significant different expression between cases and controls. The upregulation of three immune-related genes (VTCN1, NT5E and CMKLR1) remained significantly associated with disease free survival. Notably, VTCN1 and NT5E expressions were significantly associated with the risk of invasive local recurrence. Conclusions. This exploratory analysis of hormone receptor-negative, Her-2 positive DCIS with TILs ≥ 20% showed significant differences in immune-related gene expression profiles between women with subsequent IBE and controls. VTCN1 and NT5E may play an important role in immune surveillance mechanisms of DCIS and may be targeted by immune-based therapy to slow or prevent DCIS progression. These results are well worth further validation on future studies. Citation Format: Matteo Lazzeroni, Caternia Fumagalli, Federica Corso, Alberto Ranghiero, Debora Macis, Elena Guerini Rocco, Valentina Aristarco, Harriet Johansson, Aliana Guerrieri-Gonzaga, Davide Serrano, Andrea DeCensi, Sara Gandini, Massimo Barberis, Bernardo Bonanni. Identification of an immune gene expression signature for progression of breast ductal carcinoma in situ (dcis) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1705.