While we demonstrate that these MLL1 inhibitors synergize with PI3K inhibitors in PIK3CA-mutant breast cancer, this combination does not effectively target the MLL4/KMT2D COMPASS complex, which is a functionally distinct downstream PI3K effector that is essential in mediating resistance to endocrine therapies including fulvestrant (7). This evidence concerns the gene KMT2D and breast carcinoma.