This study aimed to investigate the combination of alpelisib (Piqray) and fulvestrant (Faslodex) in patients with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor 2 (HER2) negative, advanced breast cancer (BC). This study concluded that this combination provided positive outcomes for these patients. Some background The PI3K pathway normally helps cells get the energy they need to survive. Some BCs have genetic abnormalities (mutations) that help them grow and spread. A mutation in the PIK3CA gene leads to an overactivation of the PI3K pathway. This helps cancer cells survive and grow. Alpelisib is a type of targeted therapy that blocks the PI3K pathway. It can be used in combination with fulvestrant. Fulvestrant is a hormonal therapy that can be used to treat HR+ breast cancer. It blocks the action of the hormone estrogen that stimulated BC cells to grow in HR+ BC. It was previously shown that alpelisib combined with fulvestrant improves the survival without cancer worsening compared to fulvestrant alone in patients with PIK3CA-mutated, HR+, HER2- advanced BC in the short-term. However, longer-term outcomes of this combination are still under investigation.