,26 Since the efficacy of HER2-positive breast cancer patients with PIK3CA mutation receiving trastuzumab treatment is significantly reduced, and the overall survival is significantly shortened, therefore, HER2-positive breast cancer patients with PIK3CA mutation may develop resistance to chemotherapy and anti-HER2 targeted therapy, and more studies are needed to clarify the mechanism.27, 28, 29 For HR+/HER2- breast cancer, endocrine therapy is the most important treatment, but Huang D et al. found that PIK3CA mutation can lead to fulvestrant resistance.30 The gene discussed is PIK3CA; the disease is breast carcinoma.