ESR1 and breast cancer: We found that combination treatments of dactolisib or everolimus with tamoxifen also decreased cell viability in a highly synergistic manner in IntClust2 ER+ cell lines expressing high levels of AAMDC. The activity of everolimus in combination with anti-E2 therapy in clinical trials is such that it is now used routinely with anti-estrogens in the setting of metastatic BC resistant to anti-E2 treatment alone46.