The combination of endocrine therapy with most PI3K inhibitors, such as buparlisib in the BELLE-2 study and the PI3Kα inhibitors alpelisib and taselisib in the SOLAR-1 and SANDPIPER studies, respectively, has demonstrated potent anticancer effects in HR+/HER2− and AI-resistant breast cancer (Baselga et al., 2017; Baselga et al., 2018; André et al., 2019), although the pan-PI3K inhibitor pictilisib in the FERGI study showed limited efficacy in AI-resistant advanced or mBC. Here, PIK3CA is linked to breast cancer.