In line with this, we found that TP53 mutation allele frequencies were significantly higher in tumors with both mutations than TP53 mutant ESR1 WT tumors in merged metastatic tumor cohorts (Fig. 5b), suggesting a higher degree of p53 functional impairment is required to sufficiently block ER signaling in the presence of ESR1 mutations. This evidence concerns the gene ESR1 and metastatic neoplasm.