Breast cancer cutaneous lesions can present either as a local chest wall recurrence or as a site of metastatic disease and will occur in up to 30% of breast cancer patients. Salvage chemotherapy results in overall response rates of 20-30%, at best. Thus, the treatment of cutaneous lesions whether locoregional, i.e. chest wall, or a distant metastasis remains a challenge, and further investigation of novel local treatment strategies are warranted. Imiquimod, a small molecule immune response modifier, generates an immune signal similar to that of pathogenic bacteria, triggering immune activation via toll-like receptor ligand (TLR)-7. Imiquimod, has clinical activity against a variety cutaneous malignancies. Pre-clinical data from our group has shown imiquimod to augment immunity to tumor antigens in an animal model of breast cancer and induce significant tumor regression. Conventional chemotherapy, such as paclitaxel, a commonly used agent in metastatic breast cancer, may also modulate immune function. Immunostimulatory effects of paclitaxel include stimulation of IL-12 production and enhanced NK/LAK cell activity. Abraxane, a new taxane formulation, can be used in conjunction with imiquimod without compromising anti-tumor immunity as it can be administered without the immunosuppressive steroid pre-treatment required with paclitaxel. We hypothesize chemoimmunotherapy with imiquimod and abraxane can lead to higher response rates in breast cancer patients with chest wall or cutaneous metastasis than chemotherapy alone.
The specific aims of this proposal are to:
- determine the safety and therapeutic efficacy of chemoimmunotherapy with topical imiquimod and Abraxane for the treatment of breast cancer patients with recurrent chest wall disease or cutaneous metastasis,
- examine whether treatment with chemoimmunotherapy consisting of topical imiquimod and Abraxane augments endogenous tumor specific immunity, and
- assess whether chemoimmunotherapy induces molecular alterations in the tumor microenvironment that have been associated with tumor destructive adaptive immunity.