TP53 and neoplasm: In summary, mutant p53 is associated with decreased ER-α expression and downstream ER activation in ER+ primary tumors, implicating that mutant p53 may block the ability of tumor cells to acquire ESR1 mutation-induced hyperactivation or forces these cells to negate the necessity for acquisition of ESR1 mutations and thus develop ER-independent survival machinery already in primary tumors, hence hinder subsequent double mutant co-occurrence.