@article{8245,
  abstract     = {Background: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy.
Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a
major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease
progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological
phenomena.
Methods: We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of
peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive
breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as
well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers
(n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding
Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).
Results: ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+
cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration
or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells.
Conclusion: The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as
immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC
and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This
finding supports the application of trastuzumab at any stage of the disease.},
  author       = {Petricevic, Branka and Laengle, Johannes and Singer, Josef and Sachet, Monika and Fazekas, Judit and Steger, Guenther and Bartsch, Rupert and Jensen-Jarolim, Erika and Bergmann, Michael},
  issn         = {1479-5876},
  journal      = {Journal of Translational Medicine},
  publisher    = {Springer Nature},
  title        = {{Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients}},
  doi          = {10.1186/1479-5876-11-307},
  volume       = {11},
  year         = {2013},
}