A) Differential protein and phospho-protein analysis between ILC LumA and IDC LumA reveals significant lower levels of PTEN, and higher levels of Akt, phospho-Akt, EGFR, phospho-EGFR, phopsho-STAT3, and phospho-p70S6K in ILC LumA. B) A PI3K/Akt protein expression signature is significantly up-regulated in ILC tumors. See also Figure S4B–C. C) Mutation and copy number alterations in PIK3CA and PTEN D) PARADIGM identifies increased Akt activity in LumA ILC tumors. E) MEMo identified multiple mutually exclusive alterations in ILC converging on Akt signaling and associated with increased phospho-Akt and PI3K/Akt protein signature in these tumors. Hotspot are defined as follow: PIK3CA E542, E545, Q546, and H1047; ERBB2 L755, I767, V777; AKT1 E17; KRAS G12.