EORTC 90091-10093 BIG 1-12 Treat CTCs was a similarly designed phase II trial, enrolling 63 patients with non-HER2 amplified breast cancer who had at least 1 CTCs/15 mL following neoadjuvant chemotherapy and surgery, and randomized them to receive trastuzumab-based on the prior observation that patients with non-HER2 amplified breast cancer received a benefit from trastuzumab [64]—with 1 hypothesis that this benefit may stem from the targeting of HER2 positive CTCs, versus observation, with a primary endpoint of the rate of detection of CTCs at 18 weeks [65]. This evidence concerns the gene ERBB2 and breast cancer.