Vaccine Therapy in Treating Patients With Previously Treated Stage II or Stage III Breast Cancer

OBJECTIVES:

Primary

• To determine the safety and immunization efficacy of MUC1 and HER-2/neu peptide vaccines combined with CpG oligodeoxynucleotide, sargramostim (GM-CSF), or both, as immune adjuvants suspended in Freund's incomplete adjuvant in patients with previously treated stage II or III adenocarcinoma of the breast.

Secondary

• To describe the impact of immunization on clinical outcomes in patients with MUC1-positive breast cancer in terms of disease-free survival and overall survival.

OUTLINE: Patients are stratified according to Her-2/neu status (positive vs negative). Patients are randomized to 1 of 3 treatment arms.

• Arm A: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines, and sargramostim (GM-CSF) subcutaneously (SC) on day 1.
• Arm B: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A), and CpG oligodeoxynucleotide SC on day 1.
• Arm C: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A; the same as in arm B), GM-CSF, and CpG oligodeoxynucleotide SC on day 1.

In all arms, treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who complete 6 courses of treatment without disease recurrence or a second primary or intolerable toxicity will go to the observation phase of the study for up to 2 years. Patients who develop recurrent disease during the observational phase will go to the event monitoring phase for up to 2 years.

Blood samples are collected periodically. Blood samples and tissue samples from the patient's most recent surgery are used for correlative studies including immune responses to T helper and CTL epitopes by Elispot and tetramer analysis; and antigenic profiling by expression analysis of class I HLA antigens, MUC1, and HER-2 in tumor tissue.

After completion of study treatment, patients are followed periodically until disease recurrence or for up to 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Clinical stage II or III disease
• No radiographic evidence of disease at the time of enrollment
• Has undergone surgery, adjuvant chemotherapy, and/or radiotherapy

• Completed "standard first-line therapy" only (including adjuvant therapy) for breast cancer within the past 3 months and currently with no evidence of disease
• Patients with stage I breast cancer with high-risk features are eligible provided 1 of the following criteria are met:

• HER2 over-expression or amplification
• Triple-negative (i.e., no expression of ER, PR, or over-expression of HER2 on routine immunohistochemical staining)
• .
• MUC1-positive breast cancer
• HLA-A2 positive
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-2
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 75,000/μL
• ANC ≥ 1,500/uL
• Creatinine ≤ 2 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• No uncontrolled infection
• No known HIV infection
• No other circumstances (e.g., concurrent use of systemic immunosuppressants or immunocompromising condition) that in the opinion of the physician would render the patient a poor candidate for this trial
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior invasive malignancies within the past 5 years (with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Fully recovered from acute, reversible effects of any prior breast cancer therapy
• No more than 3 years since prior surgery for primary breast cancer
• Concurrent anti-estrogen therapy is allowed
• No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
• No concurrent enrollment in any other study involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, gene therapy) whether for symptom control or therapeutic intent