Safety and Efficacy Study of HER2/Neu (E75) Vaccine in Breast Cancer

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.

Inclusion Criteria:

1. Breast cancer and negative lymph nodes

2. HLA-A2+ and/or HLA-A3+ to receive the vaccine. HLA-A2-, HLA-A3- patients will be
eligible to be included in the control group.

3. Immunologically intact with a good performance status (defined below).

4. Without evidence of disease.

5. Patients may enroll while receiving appropriate hormonal therapy for their disease.

6. Completion of all standard first-line therapies (but may still be on hormonal therapy)

Exclusion Criteria:

1. HLA-A2- and/or HLA-A3- patients will not be vaccinated

2. Anergic by the Mantoux panel of recall antigens

3. Receiving immunosuppressive therapy

4. In poor health (Karnofsky <60%, ECOG >2)

5. Tbili >1.5 mg/dL and creatinine>2 mg/dL

6. Pregnancy (urine HCG)

7. Active metastatic disease

8. Involved in other experimental protocols (unless approval is first obtained by the
other study PI)

9. Refusal of standard therapies