To address these issues, a panel of ER-positive breast cancer cell lines with different PI3K pathway mutations were tested against three different PI3K pathway inhibitors, with selectivity against either the rapamycin-sensitive mammalian target of rapamycin (mTOR) complex (Everolimus/RAD001), the PI3K catalytic isoforms (BKM120) or both PI3K and mTOR (BGT226) in the presence or absence of estrogen or ER downregulation by fulvestrant. Here, ESR1 is linked to breast cancer.