The PI3K/AKT pathway has thus been long recognized as potential target for therapeutic intervention in cancer [80, 89], and very recently, a combination of the PI3K-alpha selective inhibitor BYL719 (alpelisib, Pigray®) with the estrogen receptor antagonist Fulvestrant® was approved for the treatment of advanced mammary carcinoma, as this treatment nearly doubled the median progression-free survival in PIK3CA-positive HR+/HER2+ breast cancer patients (SOLAR-1 trial, FDA approval: May 24th, 2019). This evidence concerns the gene ESR1 and breast carcinoma.