Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?

L Arnould, M Gelly, F Penault-Llorca, L Benoit, F Bonnetain, C Migeon, V Cabaret, V Fermeaux, P Bertheau, J Garnier, J-F Jeannin, B Coudert, L Arnould, M Gelly, F Penault-Llorca, L Benoit, F Bonnetain, C Migeon, V Cabaret, V Fermeaux, P Bertheau, J Garnier, J-F Jeannin, B Coudert

Abstract

This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT-NT; n=23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.

Figures

Figure 1
Figure 1
Immunohistochemical staining with NK1. Residual tumour from the TAXHER01 group (A) and from a matched tumour treated in the control group (B), both stained with NK1. The tumours of the TAXHER01 group show more cells in contact with or close to the tumour cells.
Figure 2
Figure 2
Immunohistochemical staining with CD56. Residual tumour from the TAXHER01 group (A) and from a matched tumour treated in the control group (B) both stained with CD56. The tumours of the TAXHER01 group show more cells in contact with or close to the tumour cells.
Figure 3
Figure 3
Immunohistochemical staining with Granzyme B. Residual tumour from the TAXHER01 group (A) and from a matched tumour treated in the control group (B), both stained with Granzyme B. The tumours of the TAXHER01 group show more cells in contact with or close to the tumour cells.
Figure 4
Figure 4
Immunohistochemical staining with TiA1. Residual tumour from the TAXHER01 group (A) and from a matched tumour treated in the control group (B), both stained with TiA1. The tumours of the TAXHER01 group show more cells in contact with or close to the tumour cells.

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Source: PubMed

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