This phase II trial is studying the side effects of giving topical imiquimod together with Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) to see how well it works in treating patients with advanced breast cancer. Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imiquimod together with Abraxane may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To evaluate the safety of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

II. To evaluate the anti-tumor effects of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

SECONDARY OBJECTIVES:

I. To examine whether treatment with chemoimmunotherapy consisting of topical imiquimod and Abraxane augments endogenous tumor specific immunity.

II. To assess the effect of chemoimmunotherapy on circulating transforming growth factor (TGF)-beta levels.

OUTLINE:

Patients receive Abraxane intravenously (IV) over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions once daily (QD) on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 4, 8, and 12 weeks.

Inclusion Criteria:

• Patients with advanced stage refractory breast cancer
• Progressive or relapsed disease following standard therapy with chemotherapy and/or surgery, and/or radiation
• Patients must have measurable (bi-dimensional) chest wall disease and/or cutaneous metastatic lesions
• Patients must be at least 7 days from last chemotherapy and 30 days from local radiotherapy and/or systemic steroids
• Patients on bisphosphonates, trastuzumab, lapatinib and/or hormonal therapy are eligible
• White blood cell count >= 1000/ul
• Absolute neutrophil count (ANC) >= 1200/ul
• Platelets > 75,000/ul
• Serum creatinine =< 2.0 mg/dL, a creatinine clearance > 60 ml/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 X upper limit normal (ULN)
• Total bilirubin < 2 X ULN
• Patients must have a Performance Status Score (Eastern Cooperative Oncology Group [ECOG] Scale) =< 2
• Patients must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment
• Men and women of reproductive ability must agree to contraceptive use during the study and for 1 month after imiquimod/Abraxane treatment is discontinued

Exclusion Criteria:

• Patients with prior allergic reaction to taxanes
• Patients with any clinically significant active autoimmune disease requiring active treatment with systemic steroids or other immunomodulators
• Pregnant or breast-feeding women
• Patients with peripheral neuropathy >= Grade 2