Circulating tumor-cell (CTC) count could be used to choose hormone therapy or chemotherapy as frontline treatment for patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer, according to data from the phase III STIC CTC clinical trial. In the case of discrepancy between CTC count-based treatment choice and physician’s choice of treatment, frontline chemotherapy was associated with a significant gain in overall survival.