학술논문
Clonality of circulating tumor cells in breast cancer brain metastasis patients
Document Type
article
Author
Carlotta Riebensahm; Simon A. Joosse; Malte Mohme; Annkathrin Hanssen; Jakob Matschke; Yvonne Goy; Isabell Witzel; Katrin Lamszus; Jolanthe Kropidlowski; Cordula Petersen; Anja Kolb-Kokocinski; Sascha Sauer; Kerstin Borgmann; Markus Glatzel; Volkmar Müller; Manfred Westphal; Sabine Riethdorf; Klaus Pantel; Harriet Wikman
Source
Breast Cancer Research, Vol 21, Iss 1, Pp 1-11 (2019)
Subject
Language
English
ISSN
1465-542X
Abstract
Abstract Background The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. Methods Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). Results CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p