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 þ 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 ¼ 23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT -NT; n ¼ 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.

From an established cell culture line obtained from a chemically-induced rat colon carcinoma, two sublines have been selected and isolated according to their susceptibility to trypsin-mediated detachment from plastic surfaces. Subline TR, the most resistant to the detaching effect of trypsin, gave progressive tumors in most of the syngeneic rats in which it was inoculated. Subline TS, which was easily detached by trypsin, also gave tumors in the syngeneic rats, but all these tumors disappeared within 3 or 4 weeks. Both sublines gave progressive tumors when injected into nude mice. This suggests that the parent cell line is heterogeneous and contains cell variants differing in their susceptibility to trypsin-mediated detachment from substrate and their sensitivity to host factors leading to acceptance or rejection of the inoculated tumor cells.

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