ESR1 and neoplasm: However, it is likely that, in the clinical scenario of single ER+ DTCs lodged at secondary sites, as modeled here in spontaneous metastasis assays, the level of PDGF-C produced is insufficient to generate robust tumor cell–stromal cross-talk and creation of a productive metastatic niche, delaying metastatic outgrowth until these age-related changes at secondary sites trigger ER+ DTCs to reawaken.