Lasting remission following multimodal treatment in a patient with metastatic breast cancer

Abstract

We report on a lasting remission from multimodal treatment in a patient with hepatic metastasized breast cancer. After surgical removal of a singular hepatic metastasis, the patient underwent leukapheresis of peripheral blood mononuclear cell (PBMCs). For induction chemotherapy, the patient received 2 cycles of epirubicin and paclitaxel (ET). After 1 cycle of epirubicin and ifosfamide (EI), peripheral blood stem cells were harvested. After a final cycle of ET, the patient underwent high-dose chemotherapy (HDCT; thiotepa 600 mg/m/melphalan 180 mg/m) and autologous stem cell transplantation. Once reconstitution was achieved, PBMCs were reinfused followed by i.v. application of a trifunctional antibody (TrAb) with specificities anti-EpCAMxanti-CD3. TrAbs are able to simultaneously bind tumor cells, T cells, and additionally FcgammaR type I and III+accessory cells via their Fc region. Side-effects during treatment were hematotoxicity, mucositis and gastrointestinal toxicity. TrAb treatment resulted in intermittent fever, chills, elevated liver enzymes, systemic inflammatory response syndrome and pulmonary leakage. With a follow-up period of more than 8 years the patient is still in remission (96+months). This case suggests the feasibility and efficacy of combining surgery, standard and HDCT, and subsequent immunotherapy in metastatic breast cancer. Further investigation of this approach is indicated in a subgroup of patients with oligometastatic breast cancer.

EpCAM-targeted induction of apoptosis

“…Indeed, intraperitoneal treatment with an EpCAMtargeted trAb in patients with malignant ascites resulted in the complete elimination of tumor cells in ascites as well as disappearance of ascites accumulation (35). Moreover, a recent pilot study has demonstrated the feasibility using trifunctional antibodies with anti-EpCAM X anti-CD3 and anti-Her2 X anti-CD3 in combination with high-dose chemotherapy and autologous stem cell transplantation in metastatic breast carcinoma (36). Patients treated with the trAbs showed a trend towards improved overall survival.…”