PIK3CA and breast carcinoma: While the addition of a TORC1 inhibitor prevents disease progression in patients with antiestrogen-resistant breast cancer, inhibition of TORC1 relieves negative feedback on activators of PI3K (e.g., IGF-1R, IRS-1, HER3; O’Reilly et al., 2006; Carracedo et al., 2008; Miller et al., 2009).