Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines

Ann Oncol. 2012 Jul;23(7):1788-95. doi: 10.1093/annonc/mdr484. Epub 2011 Nov 5.


Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by CD56+natural killer (NK) cells may contribute to the activity of trastuzumab in HER-2-amplified tumours. In this study, we investigated the possibility that trastuzumab might induce ADCC against HER-2-non-amplified breast cancer cells.

Methods: Induction of NK cell-mediated ADCC was examined in trastuzumab-treated HER-2-non-amplified breast cancer cell lines. HER-2 protein levels were also determined in tumour and autologous normal tissue samples from patients with HER-2 negative breast cancer.

Results: Trastuzumab induced a significant ADCC response in the HER-2-amplified HCC1954 and SKBR3 cell lines, and in all five of the non-amplified cell lines, which had low levels of detectable HER-2 by western blot (CAL-51, CAMA-1, MCF-7, T47D, and EFM19). Trastuzumab did not induce ADCC in the K562 control cell line or MDA-MB-468, which has very low levels of HER-2 detectable by enzyme-linked immunosorbent assay (ELISA) only. HER-2 protein was detected by ELISA in 14/15 patient tumour samples classified as HER-2-non-amplified. Significantly lower levels of HER-2 were detected in normal autologous tissue compared with tumour samples from the same patients.

Conclusion: Our results suggest that HER-2-non-amplified breast cancer cells, with low but detectable levels of HER-2 protein, can bind trastuzumab and initiate ADCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Amplification*
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab