Annals of Surgical Oncology

, Volume 14, Issue 12, pp 3359–3368

Quantification and Phenotypic Characterization of Circulating Tumor Cells for Monitoring Response to a Preventive HER2/neu Vaccine-Based Immunotherapy for Breast Cancer: A Pilot Study

  • Alexander Stojadinovic
  • Elizabeth A. Mittendorf
  • Jarrod P. Holmes
  • Asna Amin
  • Matthew T. Hueman
  • Sathibalan Ponniah
  • George E. Peoples
Breast Oncology Original Papers

DOI: 10.1245/s10434-007-9538-x

Cite this article as:
Stojadinovic, A., Mittendorf, E.A., Holmes, J.P. et al. Ann Surg Oncol (2007) 14: 3359. doi:10.1245/s10434-007-9538-x

Abstract

Background

Ongoing cancer vaccine trials are limited by the inability of immunologic assays to monitor clinically relevant surrogates of response. Recent advances in the ability to quantify and phenotype circulating tumor cells (CTCs) in breast cancer patients may lead to a role for CTCs in monitoring response to vaccine-based immunotherapy.

Methods

The CellSearch System (Veridex-LLC, Warren, NJ) was used to enumerate total and HER2/neu+ CTCs in 20 mL of blood from all 16 node-positive (NP) breast cancer patients active in our NP HER2/neu E75 peptide vaccine trial at the initiation of this pilot study. These patients were vaccinated with E75 (1000 μg)/GM-CSF (250 μg) monthly × 6 after completion of multimodality therapy. Mean (±SEM) number of CTCs and HER2/neu+ CTCs were compared in unmatched (n = 16) and matched (n = 9) prevaccination and postvaccination cases.

Results

CTCs were detected in 14 of 16 (88%) patients (mean: 3.4 ± 0.2 CTC/20 mL). After vaccination, a reduction in CTC/20 mL (prevaccination 3.9 ± 1.5 vs postvaccination 0.7 ± 0.4, P = .077) and HER2/neu+ CTC/20 mL (prevaccination 2.8 ± 1.0 vs postvaccination 0.5 ± 0.2, P = .048) was demonstrated. A significant delayed-type hypersensitivity (DTH) response suggesting that vaccination was effective in eliciting a peptide-specific immune response was confirmed (22.3 ± 4.1 vs 3.0 ± 2.2 [controls] mm, P < .01). All nine patients followed throughout the vaccination series also showed significant reduction in CTCs (4.8 ± 1.5 vs 0.3 ± 0.2, P < .01) and HER2/neu+ CTCs (3.0 ± 0.9 vs 0.4 ± 0.2, P = .013).

Conclusions

CTCs are readily demonstrated in posttreatment, clinically disease-free NP breast cancer patients. E75+GM-CSF vaccination appears to reduce the number of CTCs. These data suggest a potential role for this clinically validated CTC assay in assessing response to preventive vaccine-based immunotherapy, and further validation studies are underway.

Keywords

Breast cancerPeptideVaccineCirculating tumor cells

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Alexander Stojadinovic
    • 1
    • 2
  • Elizabeth A. Mittendorf
    • 3
  • Jarrod P. Holmes
    • 2
    • 4
  • Asna Amin
    • 2
    • 5
  • Matthew T. Hueman
    • 2
    • 5
  • Sathibalan Ponniah
    • 2
  • George E. Peoples
    • 2
    • 6
  1. 1.Department of SurgeryWalter Reed Army Medical CenterWashingtonUSA
  2. 2.Cancer Vaccine Development ProgramUnited States Military Cancer Institute, Uniformed Services University of the Health SciencesBethesdaUSA
  3. 3.Surgical Oncology, Department of SurgeryU.T.M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Hematology/Oncology, Department of MedicineNational Naval Medical CenterBethesdaUSA
  5. 5.General Surgery, Department of SurgeryWalter Reed Army Medical CenterWashingtonUSA
  6. 6.Surgical Oncology, Department of SurgeryBrooke Army Medical CenterHoustonUSA