Breast cancer (BrCa) is the most frequently occurring cancer in women in the Netherlands and the number one cause of death among women aged 35-55 years. Detection at the earliest stage greatly improves survival chances and diminishes the extent of the required treatment and thus related side effects. The Dutch national screening programme with mammography (X-ray) in women aged 50-75 prevents 20% of BrCa deaths annually (approximately 775). However, the screening method is faced with several disadvantages, including high false positive and negative rates. Most importantly, mammography misses ~30% of BrCa cases due to the small size of early stage tumours. In addition, screening is regarded as unpleasant and even painful by participants since breast tissue is compressed between two plates.
Our main aim is to increase quality of breast cancer screening by reducing the number of false positives and negatives and by enabling breast cancer detection in the earliest stage possible. Our novel blood-based ThromboSeq test exploits the diagnostic power of Tumour Educated Platelets (TEPs) as a better alternative to current breast cancer screening approaches. We validated computer-trained algorithms to analyse TEP RNA content and used these for (quantitative) determination of a TEP-profile detecting health or disease. Early studies in smaller cohorts proved the strength of our technology.
In 5-8% of breast cancer patients, BrCa arises due to familial genetic predispositions (i.e. BRCA1/2 mutation). These women have a 60-80% life-time risk of developing BrCa and are monitored from age 25 onwards (clinical examination, X-ray/ MRI scans). In this project we will validate the ThromboSeq test for early detection of breast cancer in a clinical population of BRCA1/2 carriers, for which we can exploit already existing infrastructures (i.e. Hereditary Breast and Ovarian cancer study Netherlands - HEBON). Since BrCa incidence is high in this population, less women need to be included to obtain statistically sufficient sample numbers. This will greatly ease study set-up and minimise the costs required for completion of the project. Moreover, improvements in the highly demanding screening protocol for premenopausal BRCA1/2 mutation carriers are highly needed.
In this nested case-control study a total of 5250 blood samples will be collected from 875 BRCA1/2 mutation carriers during a follow-up period of three years. In this period 50 incident breast cancer cases are expected to be diagnosed. The blood samples of these cases and 300 controls, randomly chosen from the cohort, will be used to calculate the sensitivity, the specificity and the positive predictive value of the new method. Additionally, we will calculate the proportion of women with a positive TEP profile at a point earlier in time than the date of detecting abnormalities during regular screening.