These results showed that the gedatolisib/fulvestrant/palbociclib triplet combination was more effective than the single agents or the fulvestrant/palbociclib doublet at blocking DNA replication and/or inducing apoptotic cell death in BC cells adapted to palbociclib and/or fulvestrant, regardless of the presence of PIK3CA mutation. The gene discussed is PIK3CA; the disease is breast cancer.