A different phenotype between primary tumor and CTCs can potentially predict poorer response to conventional anticancer therapy: for example, in metastatic BC (mBC), estrogen receptor (ER)-negative CTCs can be detected in patients diagnosed with ER-positive mBC [20] and HER2-positive CTC clones can be found in patients affected by HER2-negative mBC [21]. This evidence concerns the gene ESR1 and breast cancer.