ESR1 and breast cancer: While combined inhibition of AR and the PI3K pathway has yet to be carried out in clinical trials, combinations of PI3K inhibitors with the ER downregulator, fulvestrant, are now underway in postmenopausal patients with ER+/HER2- stage IV breast cancer who have progressed on aromatase inhibitors (BELLE-2, NCT01339442) or on the TORC1 inhibitor everolimus (BELLE-3, NCT01633060) [25].