Circulating Tumor Cells
Breast cancer (BC) therapy has fundamentally progressed in the last 30 years with the change from radical mastectomy to recent individualized local and systemic therapy regimens. By combining the modern treatment modalities, approximately 77 % of BC patie
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Circulating Tumor Cells Malgorzata Banys-Paluchowski, Helen Schneck, Natalia Krawczyk and Tanja Fehm
Abstract
Breast cancer (BC) therapy has fundamentally progressed in the last 30 years with the change from radical mastectomy to recent individualized local and systemic therapy regimens. By combining the modern treatment modalities, approximately 77 % of BC patients can be cured, still leaving potential for optimization in 23 % of cases, which will develop metastatic disease due to tumor cell dissemination despite optimal treatment. It has been known since the 19th century that most of the solid cancers shed circulating tumor cells (CTCs) into the blood circulation already at a very early stage. Based on this observation, CTCs are a surrogate marker for minimal residual disease (MRD) and precursors of metastatic disease (“seed”). Current research indicates that the phenotype and genotype differ between CTCs and primary tumor, which may result in different therapeutic responses. Therefore, characterization of CTCs may be an important step for the optimization of adjuvant and metastatic systemic treatment. Keywords
Breast cancer Circulating tumor cell characterization Biomarkers
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M. Banys-Paluchowski Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg, Germany H. Schneck N. Krawczyk T. Fehm (&) Department of Obstetrics and Gynecology, Henrich-Heine University Duesseldorf, Duesseldorf, Germany e-mail: [email protected]
Liquid biopsy
Molecular
Introduction
The presence of circulating tumor cells (CTCs) was first recognized and described by Thomas R. Ashworth in 1869 (Ashworth 1869). CTCs are cancer cells that have been released from the primary tumor into the blood stream, where they are further dispersed throughout the body (Joosse et al. 2014). In the blood circulation, CTCs may face different fates: they undergo apoptosis,
© Springer International Publishing Switzerland 2016 S. Badve and Y. Gökmen-Polar (eds.), Molecular Pathology of Breast Cancer, DOI 10.1007/978-3-319-41761-5_15
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become dormant, or survive to transmigrate into secondary organs to persist and to eventually initiate metastatic disease (Banys et al. 2012; Krawczyk et al. 2014a). Recent data indicate that CTCs are shed already at an early stage and that their presence is not solely a phenomenon associated with metastatic disease (Hüsemann et al. 2008). Further, they are considered to be genotypically and phenotypically heterogeneous cells with metastatic progenitor cell characteristics. It is assumed that 1 g tumor tissue (about 109 cells) releases about 3 106 cells per day into the blood circulation. However, given that about 99 % of these cells are supposed to die in between 30 min, only 1 % of the CTCs may persist at secondary sites in distant organs, and these cells may accumulate genetic and epigenetic alterations diverging from primary tumors (Allard et al. 2004; Meng et al. 2004a; Coumans et al. 2012). Consequently, a subfraction of an
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