Abstract 5394: Initial results from TRANSCAN ERA-NET BREMIR project: MicroRNAs expression profiling for identification of breast cancer patients at high risk to develop distant metastases
Authors: Parrella Paola , Barbano Raffaela , Evron Ella , Pasculli Barbara , Palumbo Orazio , Rendina Michelina , Stallone Raffaella , Coco Michela , Fontana Andrea , Mazza Tommaso , Copetti Massimiliano , Valori Vanna Maria , Morritti Maria , Graziano Paolo , Murgo Roberto , Maiello Evaristo , Carella Massimo , Fazio Vito Michele , Esteller Manel 
Published: August 2018

Abstract
The mortality of breast cancer (BC) is primarily caused by metastatic spread to distant organs, rendering the ability to predict, detect and eliminate metastases one of the most important challenges in patients' management. This study is aimed to evaluate the potential role of several candidate miRNAs as predictive markers of the metastatic processes. The TRANSCAN ERA-NET BREMIR project has been designed to identify miRNA biomarkers able to predict distant metastases development. The correlation of miRNAs expression with distant metastasis free survival is evaluated in a large retrospective cohort (n=302). The best candidate markers will be validated in the independent prospective cohorts which currently include 505 patients. Additionally, miRNA potentialities as circulating biomarkers for treatment monitoring and early metastases detection will be evaluated in plasma samples. The analysis of the retrospective cohort has identified miR-10b-5p, miR-10a-5p, miR-210-3p, miR-30a-5p, miR200a-3p,miR200b-3p,miR200c-3p, miR141-3p, miR-429, miR-155-5p, miR-9-3p and miR-9-5p as crucially involved in BC progression. For miR-9-5p and miR-9-3p we also found a strong inverse correlation with ER and PgR expression, suggesting that they may be directly involved in hormone regulated pathways. To identify novel miRNAs associated with tumour metastases potentials, we also executed a global miRNA profiling on a selected number of breast cancer cases by using the Affymetrix GeneChip® miRNA 4.0. In particular, we analysed 34 BC cases characterized by different outcomes: 17 non metastatic after 10-years follow-up and 17 who developed metastatic disease within 5-years follow-up. As controls, 3 Normal Breast Tissues from reductive mammoplasty, 3 in situ carcinomas and 3 breast cancer cases with synchronous metastases were also evaluated. This analysis identified 8 miRNAs differentially expressed between metastatic and non metastatic cases. The association with study endpoints is currently under evaluation on the entire retrospective cohort. Our hope is that this study will lead to the identification of novel biomarkers allowing a better management of breast cancer patients.
Citation Format: Paola Parrella, Raffaela Barbano, Ella Evron, Barbara Pasculli, Orazio Palumbo, Michelina Rendina, Raffaella Stallone, Michela Coco, Andrea Fontana, Tommaso Mazza, Massimiliano Copetti, Vanna Maria Valori, Maria Morritti, Paolo Graziano, Roberto Murgo, Evaristo Maiello, Massimo Carella, Vito Michele Fazio, Manel Esteller. Initial results from TRANSCAN ERA-NET BREMIR project: MicroRNAs expression profiling for identification of breast cancer patients at high risk to develop distant metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5394.