Importantly, while our experiments were carried out using HR+ CTC lines, analysis of a brain-tropic TNBC cell line demonstrates enrichment of hypoxic signaling, and CTC hypoxia predicts metastatic disease progression independent of subtype in a cohort comprising patients with HR+, HER2-amplified, and TNBC tumors; as such, our findings may be applicable across diverse breast cancer subtypes. Here, ERBB2 is linked to breast cancer.