Abstract
The patient, a 62-year-old woman, had been diagnosed as having human epidermal growth factor receptor 2 (HER2) type breast cancer and treated by mastectomy at 49 years of age. For treatment of a metastatic skin tumor detected 10 months after the surgery, the patient was started on trastuzumab-based chemotherapy with sequential regimen changes, and lapatinib＋capecitabine therapy. After the 5th postoperative year, the patient developed disease progression, with metastases in the contralateral, formerly unaffected breast and lung. The response to treatment with pertuzumab＋trastuzumab＋paclitaxel was rather transient, and rapid exacerbation occurred following trastuzumab emtansine (T-DM1) treatment. However, reinstitution of lapatinib＋capecitabine therapy resulted in effective disease control, and subsequent resumption of pertuzumab＋trastuzumab-based chemotherapy led to near-complete resolution of the cutaneous and breast metastases, while the lung tumor enlarged slightly. Expression of the HER2 extracellular domain (ECD), which had been elevated, normalized after resection of the lung tumor. Thereafter, the patient has shown sustained complete response (CR). The expression status of HER2 ECD and HER2 in the metastatic lesions was examined in an attempt to determine the mechanism of resistance to T-DM1. The results revealed that the metastatic lesions were actively HER2 shedding tumors, possibly explaining the greater efficacy of the tyrosine kinase-inhibitor lapatinib than of the anti-HER2 antibody drugs in this case.
