Alpelisib and fulvestrant combination has improved outcomes in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-)− advanced breast cancer (BC) who relapsed or progressed on prior endocrine therapy. The gene discussed is PIK3CA; the disease is breast cancer.