Recurrence of breast cancer can result from minimal residual disease. Havas et al. used mouse models and organoid cultures to show that residual cancer cells following tumour regression have a transcriptionally distinct state from that of normal epithelium and primary tumour cells. The transcriptomic signature of the residual cells had an altered lipid metabolism and increased levels of reactive oxygen species (ROS), features that are also observed in surviving cells in samples from patients with neoadjuvant-treated human breast cancer. The resulting increased DNA damage in the residual cells is expected to support somatic mutation-driven tumour recurrence.