Moreover, using the in vitro TGMO-based screening platform, we identified optimized low-dose synergistic drug combinations of 3 and 4 drugs with high efficacy in the tamoxifen-sensitive and -resistant subtypes of ERα + /HER2-/PI3Kα-mutant breast cancer, and with reduced toxicity in a non-cancerous breast epithelial cell line. Here, ESR1 is linked to breast carcinoma.