• The primary endpoints are the safety and optimal dosing of the vaccine to induce an in vivo peptide-specific immune response. [ Time Frame: Time period needed to determine the maximum tolerated and optimal biologic doses (30 days after each monthly dose) ] [ Designated as safety issue: Yes ]
  

• Time to recurrence is measured as a secondary outcome measure. [ Time Frame: 30 days after each monthly vaccine, then per standard of care for breast cancer. ] [ Designated as safety issue: Yes ]
  

Breast cancer is the most common malignancy and second most common cause of cancer-specific death among women in the United States. Despite advances in the diagnosis and treatment of breast cancer, one third of the women who develop the disease will die of the disease, accounting for approximately 46,300 deaths/year. While good primary therapies are available to treat early stage breast cancer, there is a substantial failure rate to these therapies in more advanced disease.

Advances in the understanding of the immune response to cancer have led to the genesis of immunotherapeutic approaches. Specifically, the development of anti-cancer vaccines holds promise as an adjuvant and preventive therapy for patients after primary surgical and medical treatment for breast cancer, but who are at a high risk for recurrence. While patients with hormone receptor positive tumors have the option to undergo hormonal therapy, recurrence is especially high among estrogen receptor/progesterone receptor (ER/PR) negative patients.

For these patients, currently there is no good treatment option after completion of primary therapy; close surveillance and watchful waiting is the standard. It is this population of patients that we have targeted with a vaccine strategy to induce cellular immunity.

In our first vaccine study, (WU # 00-2005: Phase Ib Trial of HER2/neu Peptide (E75) Vaccine in Breast Cancer Patients at High Risk for Recurrence after Surgical and Medical Therapies) we have vaccinated node-positive, HER2/neu-positive breast cancer patients with an immunogenic peptide from the HER2/neu protein mixed with a FDA-approved immunoadjuvant, GM-CSF. The study is still enrolling patients, but to date the vaccine has been safe with very limited toxicity and has been very effective at inducing an immune response to the vaccinated peptide. However, it is too early to determine if this immunity will be protective against disease recurrence.

However, with the early immunologic success of the trial, we now intend to more thoroughly study the optimal dose and schedule of vaccinations necessary to efficiently raise immunity against the peptide. In order to study these permeations, we will need to vaccinate significantly more patients; therefore, we propose to vaccinate node-negative breast patients since 75-80% of patients present with early stage breast cancer. Furthermore, we intend to vaccinate patients regardless of their HER2/neu status in order to determine the impact of prior exposure to this antigen on our ability to raise immunity against HER2/neu. Are patients with prior exposure to HER2/neu sensitized or tolerized to this antigen? This question must be answered in order to determine the usefulness of this vaccine as truly preventive in a cancer-naïve population.