In metastatic breast cancer the role of circulating tumor cells (CTCs) enumeration for predicting clinical outcome is supported by many studies, most of them dealing with strictly epithelial cells. However, it is becoming clear that CTCs are a heterogeneous cell population characterized by plasticity and including also cells which have lost the epithelial phenotype. Here we review literature data on CTC heterogeneity both at phenotype and at molecular level and discuss the possible contribute of single cell analyses in precision medicine. We conclude with some remarks about the steps still necessary to achieve clinical validity and utility when considering also CTC phenotypic and molecular heterogeneity beyond a simple enumeration.
Keywords: Breast cancer; CTC heterogeneity; CTC molecular characterization; Circulating tumor cells (CTCs); Metastasis.