• Safety and systemic toxicity as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
  
• Efficacy of denileukin diftitox in depleting T-regulatory cells (Tregs) as measured by flow cytometry [ Designated as safety issue: No ]
  

• Incidence of interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression in tumor samples as measured by immunochemistry [ Designated as safety issue: No ]
  
• Presence of circulating IL-2R in the peripheral blood as measured by ELISA [ Designated as safety issue: No ]
  
• Presence of endogenous tumor-specific immunity as measured by ELIspot [ Designated as safety issue: No ]
  
• Tumor response and progression as measured by RECIST criteria [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the safety of denileukin diftitox in patients with refractory advanced breast cancer.
• Assess the effect of this drug on peripheral blood T-regulatory suppressor cells (Tregs).

Secondary

• Determine the incidence of interleukin-2 receptor (IL-2R) expression in tumor samples from these patients.
• Correlate tumor IL-2R expression with tumor response to denileukin diftitox.
• Assess levels of circulating IL-2R before and after treatment with this drug.
• Determine the effect of this drug on endogenous tumor-specific immunity.
• Determine the potential antitumor effects of this drug in these patients.

OUTLINE: This is a nonrandomized study.

Patients receive denileukin diftitox IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study treatment. Some patients may undergo additional blood sample collection at 3 and 6 months after study treatment. T-regulatory cells (Tregs) are quantified using flow cytometry. The presence of endogenous tumor-specific immunity is evaluated using immunoenzyme techniques to detect tumor markers, including HER-2/neu, carcinoembryonic antigen (CEA), MAGE-3, and circulating interleukin-2 receptor (IL-2R). Tumor samples are collected at baseline and evaluated by immunohistochemistry for IL-2 and IL-2R (α, β, γ) expression.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of refractory advanced breast cancer

  • Progressive or relapsed disease after standard therapy

• Measurable disease that may include, but is not limited to, the bone

  • Measurable extraskeletal disease that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional CT scan OR ≥ 10 mm by spiral CT scan
  • Bidimensionally measurable chest wall disease allowed
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Male or female
• Menopausal status not specified
• ECOG performance status 0-2
• WBC > 3,000/mm³
• Absolute neutrophil count > 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
• ALT and AST ≤ 2.0 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Albumin ≥ 3.0 g/dL
• Recovered from major infections
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after completion of study treatment
• No active autoimmune disease
• No known pulmonary disease except controlled asthma
• No known hypersensitivity to diphtheria toxin or aldesleukin
• No New York Heart Association class III-IV heart disease
• No significant, active concurrent medical illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior surgical procedures
• At least 30 days since prior cytotoxic chemotherapy
• No prior treatment with denileukin diftitox or DAB (486) interleukin-2
• Concurrent bisphosphonates allowed