In HER2+ BC patients with PIK3CA mutations, combination therapies utilizing HER2 inhibitors and next-generation PI3K pathway inhibitors, such as AKT inhibitors, as well as other PI3K pathway inhibitors can overcome the therapeutic limitations of monotherapy with anti-HER2 agents in PIK3CA-mutant HER2+ BC cell lines [24]. The gene discussed is PIK3CD; the disease is breast cancer.