Abstract P3-11-16: Immunosuppressive profiles in liquid biopsy predict response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: C Salvador-Coloma, J Font De Mora, L Cordón, L Palomar, A Santaballa
Journal: Cancer Research (2019)

Abstract BACKGROUND Despite the recent advances in triple negative breast cancer (TNBC) stratification, TNBC is still a highly heterogeneous subtype that clusters distinct molecular and genetic alterations with diverse responses to neoadjuvant chemotherapy (NAC). Molecular profiling after NAC has unraveled a group of actionable targets in residual TNBC that supports the implementation of targeted therapies in a personalized manner. However, unresponsive or poor NAC responders after first line treatment are committed to poorer outcome. Therefore, early identification of poor NAC responders is essential to select patients that may benefit from alternative therapies, including initial tumor resection before chemotherapy. MATERIAL AND METHODS We have conducted a study on 37 non-metastatic TNBC patients at La Fe Hospital that were homogeneously treated with anthracycline and cyclophosphamide followed by paclitaxel. Tissue and blood-derived biopsies were obtained at diagnosis. Metabolites and miRNA exosomes in plasma were analyzed by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric and by miRNA 3.0 arrays (Affymetrix) respectively. Immunosuppressive subpopulations of cells were quantified by flow cytometry with specific markers. IDO1 in situ expression was assessed by immunohistochemistry on the tissue biopsies. RESULTS In order to identify blood-derived liquid biopsy NAC predictor biomarkers in TNBC we have studied blood circulating cells and molecules known for their immunomodulation capacity and found that eMDSC and a profile of tryptophan-derived metabolites predict NAC response. In addition, we identified a circulating exosome miRNA profile that identifies poor NAC responders. Interestingly, this profile of miRNAs target pathways involved in the immune response. IDO1 expression in the tumor inversely correlated with circulating tryptophan levels and directly associated with eMDSC. We also observed a trend correlating IDO1 expression levels with poorer response. CONCLUSIONS Our results strongly support the role of immunosuppression in TNBC poor responders and establish an easy and non-invasive tool for the early identification of poor NAC responders, opening the possibility to use alternative strategies. Acknowledgements: The authors would like to thank the Cytomics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain for its technical support. This work was partially financed with FEDER funds (CIBERONC (CB16/ 12/00284)) and AMACMA breast cancer association. Citation Format: Salvador-Coloma C, Font De Mora J, Cordón L, Palomar L, Santaballa A. Immunosuppressive profiles in liquid biopsy predict response to neoadjuvant chemotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-16.