ESR1 and neoplasm: While immune signaling pathways may provide a selective advantage within the tumor microenvironment towards immune escape (e.g. Interferon gamma response), their activation may also be responsible for cell growth and proliferation via non-canonical activation of the mTOR pathway45, which enrichment has been repeatedly reported in ESR1 mutants together with metabolic reprogramming and enhance cell growth and proliferation9,14,33,34.