Duration: 36 months
Small or medium-scale
focused research project
5 million euro
HEALTH.2013-0-1: Boosting the translation of health research projects results into innovative applications for health
About CTC-based diagnostics
In metastatic breast cancer, two proteins are essential for treatment decision making: the human epidermal growth factor receptor-2 (HER2) and the estrogen receptor (ER). The presence of these predictive factors, which act as therapy targets as well, is usually assessed on primary tumour tissue in standard daily practice. However, only specific clones within the primary tumour may have the ability to metastasize. As a result, there is a 10-40% discrepancy between the expression of HER2 and ER when comparing primary tumours with their corresponding metastases. Such discrepancies between the primary tumour and the corresponding metastases can be crucial and in worse cases lead in the choice of the wrong treatment to the individual patient. Thus, in the metastatic setting, predictive factors and therapy targets like HER2 and ER should be determined in metastatic tissue rather than falling back on the primary tumour. Since taking biopsies from metastases is often painful and frequently technically not possible, circulating tumour cells (CTCs) from peripheral blood form an attractive alternative for the assessment of predictive factors or potential targets for therapy.
As CTCs may be released by several separate tumour lesions, they possibly provide a comprehensive view of tumour characteristics, including inter- and intra-tumoural heterogeneity. Furthermore, CTCs are obtained through a simple venipuncture, which enables repetitive and real-time monitoring of a tumour’s characteristics. The CTC field is developing very rapidly and CTC-diagnostics are considered to have great promise for the practical implementation of personalized cancer treatment. In addition to the number of CTCs, which now is an established prognostic factor in several tumour types, we and others have shown that the expression of HER2 and ER differ greatly between primary breast tumours and CTCs taken at time of start treatment for metastatic disease. Therefore, knowledge of the molecular characteristics of CTCs and the heterogeneity in target protein expression is imperative to design effective (combination) therapies for the individual patient. In CareMore we will develop multiplex in situ assays to molecularly characterize CTCs, and to establish whether specific characteristics of the CTCs will lead to improved patient management with regard to choice of treatment. Ultimately, this will lead to an improved treatment outcome, reduced toxicities, and improved quality of life while reducing costs.