Long-term estrogen-deprived cells are resistant to the induction of apoptosis by phosphatidylinositol-3-kinase pathway inhibitors. Estrogen-deprived cells were treated with the indicated concentrations of (a) BGT226 or (b) BKM120 and apoptosis was measured after 4 days of treatment. Results are from at least three replicates for each treatment condition per cell line. Significant induction of apoptosis with PI3K inhibitors in parental (*P < 0.05) and long-term estrogen deprivation (LTED) lines (#P < 0.05) compared with untreated control is indicated. (c) Estrogen suppresses induction of apoptosis in LTED cells by phosphatidylinositol-3-kinase inhibitors. Cells cultured without or with estradiol were treated with BGT226 or BKM120 as indicated and apoptosis was measured after 4 days. Results are from at least three replicates for each treatment condition. Significant suppression of apoptosis by estradiol is indicated (*P < 0.05).