ESR1 and breast cancer: Interestingly, the results also showed that activation of FOXO3a(A3):ER by 4-OHT can confer resistance to the anti-proliferative effects of high levels of doxorubicin in the MDA-MB-231-FOXO3a(A3):ER, further confirming that FOXO3a function is deregulated in the drug resistant breast cancer cells.