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


METHODS
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.
Dehqanzada
Zia A
ZA
Clinical Breast Care Project, Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia, USA.
Storrer
Catherine E
CE
Hueman
Matthew T
MT
Foley
Rebecca J
RJ
Harris
Katie A
KA
Jama
Yusuf H
YH
Kao
Tzu-Cheg
TC
Shriver
Craig D
CD
Ponniah
Sathibalan
S
Peoples
George E
GE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology* / Q000517:prevention & control; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D018796:Immunoconjugates; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate
D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D018932:Chemokine CCL2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018796:Immunoconjugates; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C474513:HER-2 peptide E75 (369-377), human