Longitudinal Profiling Of Plasma Derived Extracellular Vesicles (Evs) From Women Presenting With Metastatic Triple-Negative Breast Cancer (Mtnbc) Informs On Metastatic Location And Treatment Outcome

Background: Women presenting with Triple Negative Breast Cancer (TNBC) have an increased risk of recurring at distant visceral metastatic sites such as brain, lungs and liver rather than bone compared to oestrogen-receptor-positive breast cancer. (Rakha et al., 2011, Wood 2004). The preferential homing of TNBC cancer cells to these sites is not clearly understood, but is increasingly being attributed to the ability of extracellular vesicles (EVs) released by chemoresistant cancer cells to circulate to distant sites creating metastatic niches and paving the way for organ-specific metastases. Hypothesis: We hypothesise that the physical EV properties, macromolecular and proteomic content of these EVs could potentially determine the risk of metastasis and align with these “preferred” metastatic locations. Methodology: This project uses nanoparticle tracking analysis (NTA), infra-red and mass spectroscopy to generate unique patient-specific EV longitudinal signatures of women diagnosed with organ defined metastatic TNBC. These signatures hold potential as “unique identifiers” of clinically documented organ-specific metastases. All profiles generated are compared longitudinally to the patient9s initial baseline sample and also to age matched female control plasma samples. Results and Conclusions: Preliminary results have developed SOPs to (i) successfully enrich for EVs from patient plasma samples and (ii) employ nanoparticle tracking analysis, infra-red and mass spectroscopic profiling to develop unique longitudinal patient specific EV signatures. The longitudinal profiling of EV signatures from patients with metastatic TNBC will potentially (a) predict response to therapy, (b) uniquely identify risk of and potential location of metastatic site/sites and (c) inform on patient outcome. Following this multidisciplinary profiling of our mTNBC, our remit is to recapitulate this profiling into the primary TNBC setting to identify potential sites of organ specific metastases ahead of any detection on an x-ray or scan, thereby informing on clinical management. Citation Format: Sinead Lindsay, Jennifer McIntyre, Luke Gubbins, Martina Smith, Laura Kerr, Emma Kavanagh, Michaela J. Higgins, Bryan Hennelly, Paul Dowling, Hugh Byrne, Amanda McCann. Longitudinal profiling of plasma derived extracellular vesicles (EVs) from women presenting with metastatic triple-negative breast cancer (mTNBC) informs on metastatic location and treatment outcome [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 1060.