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. 1999 Dec 8;82(1):46–51. doi: 10.1054/bjoc.1999.0875

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

H Kunisue 1,5, J Kurebayashi 1, T Otsuki 2, C K Tang 3, M Kurosumi 4, S Yamamoto 1, K Tanaka 1, H Doihara 5, N Shimizu 5, H Sonoo 1
PMCID: PMC2363211  PMID: 10638965

Abstract

Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, butmost of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combinedtherapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect ofcombined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, onthe cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combinedtreatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, butshowed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, whichexpress no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1–S blockadeand apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for thetreatment of patients with breast cancer expressing both ER and HER2. © 2000 Cancer Research Campaign

Keywords: anti-HER2 antibody, anti-oestrogen, breast cancer, additive effect, apoptosis

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Selected References

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