Advances in the Characterization of Circulating Tumor Cells in Metastatic Breast Cancer: Single Cell Analyses and Interactions, and Patient-Derived Models for Drug Testing.

Metastasis is the major cause of breast cancer death worldwide. In metastatic breast cancer, circulating tumor cells (CTCs) can be captured from patient blood samples sequentially over time and thereby serve as surrogates to assess the biology of surviving cancer cells that may still persist in solitary or multiple metastatic sites following treatment. CTCs may thus function as potential real-time decision-making guides for selecting appropriate therapies during the course of disease or for the development and testing of new treatments. The heterogeneous nature of CTCs warrants the use of single cell platforms to better inform our understanding of these cancer cells. Current techniques for single cell analyses and techniques for investigating interactions between cancer and immune cells are discussed. In addition, methodologies for growing patient-derived CTCs in vitro or propagating them in vivo to facilitate CTC drug testing are reviewed. We advocate the use of CTCs in appropriate microenvironments to appraise the effectiveness of cancer chemotherapies, immunotherapies, and for the development of new cancer treatments, fundamental to personalizing and improving the clinical management of metastatic breast cancer.