A 51-year-old premenopausal woman was diagnosed with HER2-positive breast cancer….Due to abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in the patient, treatment was changed to the mammalian target of rapamycin (mTOR) inhibitor combined with the anti-HER-2 agents inetetamab and paclitaxel, while partial response (PR) was evaluated after 6 cycles of treatment. As the patient was hormone receptor (HR) positive, treatment was changed to the inetetamab + rapamycin + exemestane regimen. The lesion continued to shrink and PR was evaluated for 8 cycles....A phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation in trastuzumab-treated metastatic HER2-positive breast cancer female had a long PFS by treating with the mammalian target of rapamycin inhibitor in combination with the anti-HER-2 agent inetetamab.