1. ¹Department of Pathology, Centre G-F Leclerc, Dijon 21000, France
2. ²Centre J Perrin, Clermont 63011, France
3. ³Department of Surgery, Centre G-F Leclerc, Dijon 21000, France
4. ⁴Department of Statistics Centre G-F Leclerc, Dijon 21000, France
5. ⁵Centre A Vautrin, Nancy 54000, France
6. ⁶Centre O Lambret, Lille 59020, France
7. ⁷CHU, Limoge 87000, France
8. ⁸CHU Saint Louis, Paris 75010, France
9. ⁹Laboratoire Roche, Neuilly 92521, France
10. ¹⁰EPHE, INSERM U517, and IFR 100, Faculté de médecine, Dijon 21063, France
11. ¹¹Department of Oncology, Centre G-F Leclerc, Dijon 21000, France

Correspondence: Dr L Arnould, Centre Georges-François Leclerc, 1 rue Prof. Marion, 21000 Dijon Cedex, France. E-mail: larnould@dijon.fnclcc.fr

Received 2 August 2005; Revised 23 November 2005; Accepted 29 November 2005; Published online 10 January 2006.

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.