Mechanistically, Cd‐induced MTA depletion specifically increased DOT1L methyltransferase activity and H3K79me1 levels in the PAK2 promoter region, inducing the expression of PAK2, which contributed to the autophagic flux blockade required for BC progression in Cd‐exposed BC cells and transgenic MMTV‐ErbB2 mice. The gene discussed is ERBB2; the disease is breast cancer.