Hence, PI3K hyperactivation (either by means of constant stimulation, or by means of PTEN deficiency, which can often be found in BRCA1-mutated tumors [120]) coupled with E2 stimulation (which is tissue-specific and generally elevated in BRCA1 mutation carriers) may lead to NRF2 accumulation in BRCA1−/− pre-tumor cells (germline first hit and somatic second hit), helping the cell to escape ROS-induced cell death. The gene discussed is NFE2L2; the disease is neoplasm.