Long-term, 25-year Survival Following Surgery and Immune Cell Therapy Combined with Chemotherapy for HER2-Positive Metastatic Breast Cancer

The surgical cure rate for breast cancer is relatively high among the various cancers thanks to recent advances in perioperative hormonal therapy and chemotherapy.However, the 10-year survival rate for stage 4 breast cancer is only 16% in Japan.Here we report a case of 25-year survival following primary right radical mastectomy with axillary lymph node dissection at age 46 years (in 1996) and subsequent immunotherapy and chemotherapy.Pathological diagnosis was stage 3A (T3aN2M0), and histochemical diagnosis was estrogen receptor(-), progesterone receptor(+), HER2(+).During postoperative year 1 (POY1), chemotherapy and focal radiation therapy were added for a solitary metastatic lesion to a right cervical lymph node.Continuous chemotherapy for HER2(+) metastatic breast cancer (MBC) was performed for 8 years.In POY8, side effects of chemotherapy became intolerable, tumor marker levels increased, and lymphodepletion developed.Following immune cell therapy with activated T lymphocytes (ATL)she recovered completely with no adverse events for the next 10 years.In POY18, a second, massive administration of ATL was required because of right-sided malignant pleural effusion.She recovered again to ECOG performance status(PS) 0 at 1 year after the immunotherapy combined with chemotherapy.Twenty-five years after initial surgery, the patient continues to be well.We discuss several important factors for predicting the effectiveness of immune cell therapy combined with chemotherapy during long-term follow-up.The most important are lymphodepletion and trends in the CD4/CD8 ratio, and other considerations are the effectiveness of the chemotherapeutic agents combined with immune cell therapy, tumor markers, and ECOG PS.