Prolonged Disease Control after Myeloablative Chemotherapy, Autologous Transplantation and Immunotherapy in High-risk Early Breast Cancer

Background: Failure to eradicate all cancer stem cells, lymphocytopenia, and high levels of vascular endothelial growth factor (VEGF) may explain the limited efficacy of high dose-chemotherapy (HDCT) with peripheral progenitor cell transplantation (PBPCT) in high-risk early breast cancer with more than 10 axillary nodes (HRBC). Patients and Methods: With the aim of increasing patient's lymphocyte count and reducing VEGF wich could translate into an improved immune function and a better clinical outcome, patients with HRBC, received HDCT, PBPCT and immunotherapy with interleukin-2 (IL-2) and 13-cis retinoic acid (RA). Results: A total of 30 HRBC patients were entered into the study. Grade 4 hematological toxicity was universal, while major adverse effects of IL-2 were fever, rash and autoimmune reactions. After a median follow-up of 61 months, immune function improved with a statistically significant increase of lymphocyte count and a decrease in VEGF levels. This translated into ail unexpected 5-year relapse-free and overall survival rates of 76% and 85%, respectively. Conclusion: These data show that IL-2 and RA administration after HDCT and PBPCT is feasible and, as well as giving a statistically significant improvement in lymphocyte count and a decrease of VEGF, also seems to improve the expected clinical outcome.