Using breast cancer cell lines and xenograft models we show that RMC-6272 causes apoptosis specifically in PIK3CA and PTEN mutant ER+/HER2- breast cancer cell lines through suppression of the rapamycin resistant, mTORC1 substrate 4EBP1 and reduction of the pro-survival protein MCL1. Here, ESR1 is linked to breast carcinoma.