Abstract 1129
Background
Tumour cell induced platelet aggregation (TCIPA) increases the metastatic potential of cancer. Mechanisms include protection of tumour cells from immune destruction, interaction of platelet receptors with tumour ligands to facilitate adhesion, enrichment of the tumour microenvironment to promote tumour cell extravasation and proliferation. Reducing these interactions using antiplatelet agents could reduce metastatic progression. This study investigated the effect of Ticagrelor and aspirin on TCIPA in metastatic breast and colorectal cancer patients, compared to healthy controls.
Methods
Participants in this randomised, crossover study received aspirin or Ticagrelor for 2 weeks, followed by 2 weeks washout and crossover to the other monotherapy, before completing 2 weeks of dual therapy. Platelet rich plasma was prepared from blood samples at each time point. Light transmission aggregometry measured spontaneous aggregation of the platelets over 30 minutes without the addition of exogenous agonists. Flow cytometry measured the activation markers P-selectin and fibrinogen binding on unstimulated platelets.
Results
20 healthy, 10 breast and 6 colorectal cancer participants completed the study. Untreated platelets from colorectal patients had higher spontaneous aggregation (14.8±2.6%) than breast cancer (8.7±1%) or healthy platelets (8.1±0.9% p = 0.007). This was reduced by Ticagrelor (7.7±3.3% p = 0.01). Untreated platelets from patients with colorectal cancer had higher expression of P-selectin compared to platelets from healthy donors (14.2±1.3% vs 21.5±3.6% p = 0.03). Untreated platelets from breast patients had increased fibrinogen binding (49.5±7.8%) compared to healthy platelets (31.4±4.2% p = 0.03). This was reduced by Ticagrelor (26.7±5.2% p = 0.04) and dual therapy (31.4±6.9% p = 0.01).
Conclusions
This study demonstrated that platelets from breast and colorectal cancer patients are hyperactive compared to healthy donors. Ticagrelor reduces aggregation in platelets from patients with colorectal cancer, and as monotherapy and dual therapy can reduce platelet activation in patients with breast cancer. The pilot study indicates Ticagrelor may reduce TCIPA in cancer patients and could be used to decrease metastatic spread.
Clinical trial identification
EudraCT: 2014‐004049‐29, Start date:10‐03‐2015.
Editorial acknowledgement
Legal entity responsible for the study
University of Leicester.
Funding
AstraZeneca.
Disclosure
A. Thomas: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. A. Goodall: Research grant / Funding (institution): Hoffmann La Roche; Research grant / Funding (institution): AstraZeneca. D. Adlam: Research grant / Funding (institution): Abbott Vascular Inc; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
2036 - Salivary metabolomics for colorectal cancer detection
Presenter: Hiroshi Kuwabara
Session: Poster Display session 3
Resources:
Abstract
1868 - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Presenter: Veronika Voronova
Session: Poster Display session 3
Resources:
Abstract
3655 - Liquid biopsy assays using combined circulating tumor cells and circulating tumor DNA in the same patients for the diagnosis of primary lung cancer
Presenter: Yongjoon Suh
Session: Poster Display session 3
Resources:
Abstract
3685 - Peripheral Cytotoxic T Cell Correlates with Tumor Mutational Burden and is Predictive for Progression Free Survival in Advanced Breast Cancer
Presenter: Xiao-ran Liu
Session: Poster Display session 3
Resources:
Abstract
1050 - Splenic Metabolic Activity as Biomarker in Cervical Cancer
Presenter: Emiel De Jaeghere
Session: Poster Display session 3
Resources:
Abstract
1413 - Identification of distinct subtypes revealing prognostic and therapeutic relevance in diffuse type gastric cancer
Presenter: Seon-Kyu Kim
Session: Poster Display session 3
Resources:
Abstract
2140 - Recurrence risk evaluation in stage IB/IIA gastric cancer with TP53 codon 72 polymorphisms
Presenter: Satoshi Nishizuka
Session: Poster Display session 3
Resources:
Abstract
1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Presenter: Yongcong Yan
Session: Poster Display session 3
Resources:
Abstract
1196 - Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Presenter: Wenxin Xu
Session: Poster Display session 3
Resources:
Abstract
2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Presenter: Katharina Nekolla
Session: Poster Display session 3
Resources:
Abstract