ESR1 and breast cancer: The strongest and most coherent signals arise in breast cancer—particularly ER-positive disease—where chemotypes engaging VEGFR-2/aromatase/ER and mitochondrial/caspase axes drive apoptosis and G2/M arrest; complementary signals are seen in lung models (topoisomerase I/CDK2, Hsp90, PI3K/Akt/mTOR, with autophagy as a modulatory node).