Trastuzumab decreases the number of circulating and disseminated tumor cells despite trastuzumab resistance of the primary tumor

Cancer Lett. 2008 Feb 18;260(1-2):198-208. doi: 10.1016/j.canlet.2007.10.043. Epub 2007 Dec 21.

Abstract

We have recently shown that despite of the fact that the ErbB2-positive JIMT-1 human breast cancer cells intrinsically resistant to trastuzumab in vitro, trastuzumab inhibited the outgrowth of early phase JIMT-1 xenografts in SCID mice via antibody-dependent cellular cytotoxicity (ADCC). Here we show that trastuzumab significantly reduces the number of circulating and disseminated tumor cells (CTCs and DTCs) in this xenograft model system at a time when the primary tumor is already unresponsive to trastuzumab. This observation suggests that ErbB2 positive CTCs and DTCs might be sensitive to trastuzumab-mediated ADCC even if when the primary tumor is already non-responsive. Thus, trastuzumab treatment might also be beneficial in the case of patients with breast cancer that is already trastuzumab resistant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow / drug effects*
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chromosomes, Human, X
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Histocompatibility Antigens Class I / analysis
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leukocyte Common Antigens / analysis
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / drug effects*
  • Neoplastic Cells, Circulating / immunology
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology
  • Rituximab
  • Time Factors
  • Trastuzumab
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Histocompatibility Antigens Class I
  • Rituximab
  • EGFR protein, human
  • ErbB Receptors
  • Leukocyte Common Antigens
  • Ptprc protein, mouse
  • Trastuzumab