Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients

Clin Cancer Res. 2006 Jan 15;12(2):478-86. doi: 10.1158/1078-0432.CCR-05-1425.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / prevention & control
  • Cancer Vaccines / therapeutic use*
  • Chemokine CCL2 / metabolism*
  • Disease Progression
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Immunity, Cellular
  • Immunoconjugates
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Middle Aged
  • Neoplasm Staging
  • Peptide Fragments / immunology*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Cancer Vaccines
  • Chemokine CCL2
  • HER-2 peptide E75 (369-377), human
  • Immunoconjugates
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptor, ErbB-2