TY - JOUR
T1 - Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients
AU - Dehqanzada, Zia A.
AU - Storrer, Catherine E.
AU - Hueman, Matthew T.
AU - Foley, Rebecca J.
AU - Harris, Katie A.
AU - Jama, Yusuf H.
AU - Kao, Tzu Cheg
AU - Shriver, Craig D.
AU - Ponniah, Sathibalan
AU - Peoples, George E.
PY - 2006/1/15
Y1 - 2006/1/15
N2 - 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 HER-2/neu E75 vaccine. Experimental Design: We measured MCP-1 levels in 32 HER-2/neu+ breast cancer patients before and after vaccination with a HER-2/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 HER-2 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 HER-2/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.
AB - 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 HER-2/neu E75 vaccine. Experimental Design: We measured MCP-1 levels in 32 HER-2/neu+ breast cancer patients before and after vaccination with a HER-2/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 HER-2 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 HER-2/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.
UR - http://www.scopus.com/inward/record.url?scp=31544451057&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-05-1425
DO - 10.1158/1078-0432.CCR-05-1425
M3 - Article
C2 - 16428490
AN - SCOPUS:31544451057
SN - 1078-0432
VL - 12
SP - 478
EP - 486
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -