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| Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? |
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| Author(s): Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, Cabaret V, Fermeaux V, Bertheau P, Garnier J, Jeannin JF, Coudert B |
| Source: BRITISH JOURNAL OF CANCER Volume: 94 Issue: 2 Pages: 259-267 Published: JAN 30 2006 |
| Times Cited: 65 References: 39 |
| 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 IHC3+ 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 TiAI. 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 TiAI 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. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Arnould, L (reprint author), Ctr Georges Francois Leclerc, Dept Pathol, 1 Rue Prof Marion, F-21000 Dijon, France |
Addresses:
1. Ctr Georges Francois Leclerc, Dept Pathol, F-21000 Dijon, France
2. Ctr J Perrin, F-63011 Clermont Ferrand, France
3. Ctr GF Leclerc, Dept Surg, F-21000 Dijon, France
4. Ctr GF Leclerc, Dept Stat, F-21000 Dijon, France
5. Ctr Alexis Vautrin, F-54000 Nancy, France
6. Ctr Oscar Lambret, F-59020 Lille, France
7. CHU, F-87000 Limoges, France
8. CHU St Louis, F-75010 Paris, France
9. Lab Roche, F-92521 Neuilly, France
10. EPHE, INSERM, U517, F-21063 Dijon, France
11. Fac Med, IFR 100, F-21063 Dijon, France
12. Ctr GF Leclerc, Dept Oncol, F-21000 Dijon, France |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Oncology |
| IDS Number: 010JF |
| ISSN: 0007-0920 |
| DOI: 10.1038/sj.bjc.6602930 |
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