Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogenon breast cancer cells expressing both oestrogen receptors and HER2

Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-po sitive breast carcinomas, but most of these tumours become resistant to ant i-oestrogen. it has been suggested that anti-oestrogen therapy may induce a HER2 signalling pathway in breast cancer cells and this may cause resistan ce to anti-oestrogen. Thus, it is conceivable that combined therapy with an ti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect of combined treatment with a humanized a nti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrog en, ICI 182,780, on the cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2, The combined t reatment enhanced the growth inhibitory effect on ML-20 cells, which expres s a high level of ER and a moderate level of HER2, but showed no additive e ffect on either KPL-4 cells, which express no ER and a moderate level of HE R2, or MDA-MB-231 cells, which express no ER and a low level of HERP. It is also suggested that both the antibody and anti-oestrogen induce a G1-S blo ckade and apoptosis. These findings indicate that combined treatment with a nti-HER2 antibody,and anti-oestrogen may be useful for the treatment of pat ients with breast cancer expressing both ER and HERP. (C) 2000 Cancer Resea rch Campaign.