In MDA-AB-361, an ER+/HER2+ BC cell line bearing PIK3CA-mutations that confer resistance to HER2 therapy, triple-combination therapy with fulvestrant (a selective estrogen receptor degrader), lapatinib, and ipatasertib (an Akt inhibitor) demonstrated enhanced antiproliferative ability in comparison to double-combination therapy with fulvestrant and lapatinib. Here, ESR1 is linked to breast cancer.