This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.

Gallbladder cancer is an uncommon cancer that has traditionally been associated with a poor prognosis. In the era of laparoscopic cholecystectomy, incidental gallbladder cancer has dramatically increased and now constitutes the major way patients present with gallbladder cancer. While patients with incidental gallbladder cancer have a better survival than patients with nonincidental gallbladder cancer, incidental gallbladder cancer can be associated with a varied prognosis. Imaging with computed tomography (CT), magnetic resonance imaging (MRI), and [18]F-fluorodeoxyglucose (FDG) positron emission tomography (PET), as well as diagnostic laparoscopy, all have varying roles in the workup of patients with incidental gallbladder cancer. For patients with T1b, T2, and T3 incidental gallbladder cancer re-resection is generally recommended. At re-exploration, many patients with incidental gallbladder cancer will have residual disease. Definitive oncologic management requires re-resection of the liver, portal lymphadenectomy, and attention to the common bile duct. The extent of the hepatic resection should be dictated by the ability to achieve a microscopically negative (R0) margin. Routine resection of the common bile duct is unnecessary but should be undertaken in the setting of a positive cystic duct margin. If an incidental gallbladder cancer is discovered at the time of surgery, whether the surgeon should directly proceed with a more definitive oncologic operation should depend on the surgeon's skill-set and experience. Gallbladder cancer has a propensity to recur. Although data for adjuvant therapy following resection are limited, some data do suggest a survival benefit for adjuvant chemoradiation therapy. Management of patients with gallbladder cancer requires a multidisciplinary approach with input from a surgeon skilled in hepatobiliary surgery.

Purpose: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. Experimental Design: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. Results: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. Conclusions: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.Breast cancer is the most common cancer diagnosis in women and the second leading cause of cancer-related death among women.7 Despite advances in standard treatment, a significant proportion of breast cancer patients will ultimately die from recurrent disease, especially aggressive subsets, such as those overexpressing HER2/neu. HER2/neu is a protooncogene expressed in many epithelial malignancies (1). Overexpression of HER2/neu is found in 20% to 25% of breast cancer and confers a poor prognosis (2).Novel approaches are needed to further improve outcomes among breast cancer patients, and one such approach is immunotherapy. Trastuzumab is a monoclonal antibody that targets the HER2/neu protein and is an effective treatment of metastatic breast cancer (3). Several recent large trials have shown that adjuvant trastuzumab decreases recurrence rates compared with chemotherapy alone (4 -6).Another mode of immunotherapy in treating cancer is vaccines. Tumor-associated antigens are proteins expressed by 7 Ries LAG, Harkins D, Krapcho M, et al. (eds.).