In a phase III trial enrolling PIK3CA mutant luminal breast cancer patients progressing to hormonal treatment, adding alpelisib, a specific p110α PIK3CA inhibitor, to fulvestrant significantly improved antitumor activity (response rate 26.6% vs. 12.8%) and progression-free survival (11 vs. 5.7 months) over a combination of placebo plus fulvestrant, leading to its regulatory approval. Here, PIK3CA is linked to breast cancer.