• 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 ]

• Safety and systemic toxicity as measured by CTCAE v3.0
• Efficacy of denileukin diftitox in depleting T-regulatory cells (Tregs) as measured by flow cytometry

• 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 ]

• Incidence of interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression in tumor samples as measured by immunochemistry
• Presence of circulating IL-2R in the peripheral blood as measured by ELISA
• Presence of endogenous tumor-specific immunity as measured by ELIspot
• Tumor response and progression as measured by RECIST criteria

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to breast cancer cells.

PURPOSE: This phase I/II trial is studying the side effects of denileukin diftitox and to see how well it works in treating patients with advanced breast cancer that did not respond to previous treatment.

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 15 patients will be accrued for this study.

• Biological: denileukin diftitox
• Genetic: protein expression analysis
• Other: flow cytometry
• Other: immunoenzyme technique
• Other: immunohistochemistry staining method
• Other: laboratory biomarker analysis

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)
• Total bilirubin ≤ 1.5 times ULN
• Albumin ≥ 3.0 g/dL
• Recovered from major infections
• Not pregnant or nursing
• 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 14 days since prior cytotoxic chemotherapy
• No prior treatment with denileukin diftitox or DAB (486) interleukin-2
• Concurrent bisphosphonates allowed