Journal
BRITISH JOURNAL OF CANCER
Volume 94, Issue 2, Pages 259-267Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6602930
Keywords
primary systemic therapy; trastuzumab; ADCC; MoA
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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.
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