ESR1 and breast carcinoma: Interestingly, although up to 80% of BRCA1 mutant breast cancers are ER negative, estrogen positively regulates Nrf2 transcriptional activity through activation of PI3K/Akt signaling allowing BRCA1-null cells to detoxify high ROS levels and accumulate additional genetic aberrations that may contribute to tumorigenesis (73, 74).