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Correlations between Serum Monocyte Chemotactic Protein-1 Levels, Clinical Prognostic Factors, and HER-2/neu Vaccine-Related Immunity in Breast Cancer Patients

Authors' Affiliations: ¹ Clinical Breast Care Project, Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia, and ² Clinical Breast Care Project, Immunology and Research Center, and ³ Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Requests for reprints: George E. Peoples, Clinical Breast Care Project, Immunology and Research Center, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Building 139, Bethesda, MD 20814. Phone: 202-782-9692; Fax: 301-493-6840; E-mail: george.peoples{at}na.amedd.army.mil.

Purpose: We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine.

Experimental Design: We measured MCP-1 levels in 32 /neu⁺ breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored.

Results: Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (<250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with <50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with >30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8⁺ T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination.

Conclusions: High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.

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