Effect of trastuzumab on antibody-dependent cellular cytotoxicity (ADCC) in HER2 nonamplified (non-amp) breast cancer (BC) cells.

659 Background: Trastuzumab (T) is currently indicated for the treatment of Her-2 positive breast cancers. The NSABP B-31 adjuvant trial suggested a possible clinical benefit for the addition of T to chemotherapy in patients whose tumors were Her-2 negative (low Her-2 expressing, non-amplified by FISH). ADCC mediated by CD56+ natural killer (NK) cells is known to play a role in response to T in Her-2 positive tumors. To investigate the possibility that T may induce ADCC against Her-2 negative tumors, we examined NK cell-mediated ADCC in T-treated, non-amp, low Her-2 expressing BC cell lines. Methods: A membrane/cytosol separation kit and immunoblotting were used to assess surface Her-2 levels in the non-amp BC cell lines CAMA-1, T47D, EFM19, MCF-7 and CAL-51. The positive control for Her-2 expression and amplification was HCC1954 and MDA-MB-468 was the negative control. PBMCs were isolated from whole blood of 8 healthy volunteers using a Ficoll-Plaque method. CD56+ NK cells were isolated from the PBMC fra...