A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors.

Pancreatic and biliary cancers are relatively resistant to chemotherapy and radiation and may therefore provide an opportunity for testing the potential of immunotherapy. MUC1 is an epithelial cell glycoprotein that is highly overexpressed and aberrantly glycosylated in many adenocarcinomas, including pancreatic tumors, providing a tumor specific antigen and target. We performed a Phase I/II clinical trial of a MUC1 peptide-loaded DC vaccine in 12 pancreatic and biliary cancer patients following resection of their primary tumors. The primary endpoints were vaccine toxicity and immunogenicity and the secondary endpoint was clinical outcome. The vaccine was well tolerated and no toxicity was observed. Three patients had pre-existing MUC1 antibody responses that remained stable post vaccination. MUC1-specific T cell responses were difficult to evaluate due to increases in activity of all CD8 and CD4 T cells following each vaccination. Prior to vaccination, patients entered onto this trial had a significantly higher percentage of FoxP3+CD4+ T cells compared to age matched healthy controls. The percentage of these cells also increased transiently following each injection, returning to baseline or below before the next injection. Vaccinated patients have been followed for over four years and four of the twelve patients are alive, all without evidence of recurrence. Study of the immune parameters in long-term survivors several years after vaccination may yield the sought after immune correlates of clinical responses that analysis of immune responses shortly after vaccination has not revealed.

Chemoprevention of breast cancer in postmenopausal women.

In the United States, an estimated 211,240 new cases of breast cancer were diagnosed in 2005 and approximately 40,410 deaths occurred. In recent years, a number of randomized prospective trials have investigated the use of antiestrogens as a means to reduce the incidence of breast cancer. We aim to describe the results of these trials as they pertain to postmenopausal women. In the Breast Cancer Prevention Trial and the International Breast Cancer Intervention Study-I, tamoxifen reduced the risk of invasive breast cancer by 55% and 30%, respectively, among older participants. However, tamoxifen is associated with adverse events including thromboembolic disease and endometrial cancer. The Multiple Outcomes of Raloxifene Evaluation, aimed primarily at evaluating the use of raloxifene for the prevention of osteoporosis, demonstrated a 72% decreased breast cancer risk. Side effects of raloxifene include thromboembolic events, but not endometrial cancer. Results from the Study of Tamoxifen and Raloxifene trial comparing these two agents are expected in mid-2006. Ongoing chemoprevention trials are evaluating the use of the aromatase inhibitors. At present, tamoxifen is the only FDA-approved agent for breast cancer risk reduction. Decisions regarding its use must remain highly individualized, involving careful consideration of its risks versus benefits.