Can Circulating Tumor Cells Predict Resistance in Metastatic Breast Cancer?

摘要

Circulating tumor cell (CTC) enumeration provides prognostic but not predictive information for chemotherapy in metastatic breast cancer. Because CTC measurement is reproducible and allows molecular profiling, an assay to assess endocrine resistance was developed. Whether this CTC-based assay can be used to reliably select endocrine therapy must be tested. In this issue of Clinical Cancer Research, Paoletti and colleagues (1) describe the development of a Circulating Tumor Cell-Endocrine Therapy Index (CTC-ETI), an assay based on both enumeration of CTC and measurement of protein expression using immunofluorescence staining of CTC. CTCs are malignant cells found in peripheral blood that originate from primary or metastatic cancer tissue (Fig. 1; ref. 2). Because circulating cancer cells are extremely rare, their detection requires enrichment techniques based on biologic properties (e.g., tumor-specific cell-surface antigens or protein secretion) or physical characteristics (e.g., size, density, deformability, or electric charges) of tumor cells (2). Paoletti and colleagues used the CellSearch system, the only FDA-approved CTC enumeration technology for metastatic breast cancer, as the basis for their work. This technology uses epithelial cell-adhesion molecule-based (EpCAM) immunomagnetic beads for enrichment of CTC, followed by positive immunofluorescence staining for a cytoker-atin epithelial marker (CK-8, 18, and 19) and a nuclear dye (DAPI) and negative staining for common leukocyte antigen (CD45; ref. 3). Over the past decade, numerous clinical trials have investigated the prognostic role of CTC detection in metastatic breast cancer (3-5). A recent individual patient data meta-analysis, using 1,944 patients with metastatic breast cancer from 20 studies, confirmed the independent poor prognosis of an elevated CTC count of >5/ 7.5 mL of whole blood in terms of progression-free survival and overall survival compared with a baseline CTC count of <5/7.5 mL (6). When compared with imaging studies, CTC assessment was more reproducible (interobserver variability -0.7%) and was an earlier marker of disease progression (4). In contrast with tumor markers such as CA15-3 and CA27.29, CTC does not reflect tumor bulk (4).