In all breast cancer subtypes, there was an increased co-mutation frequency in alpelisib off-label cohort compared to on-label cohort in CHEK2 and ERBB2, and increased co-mutation frequency in alpelisib on- and off-label cohorts compared to PIK3CA-WT in CHEK2, HRAS, TP53, CDH1, and NF1. Here, HRAS is linked to breast cancer.