title: Trastuzumab (Herceptin®): overcoming resistance in HER2-overexpressing breast cancer models.
abstract: Evaluation of: Fujimoto-Ouchi K, Sekiguchi F, Yamamoto K et al.: Preclinical study of prolonged administration of trastuzumab as combination therapy after disease progression during trastuzumab monotherapy. Cancer Chemother. Pharmacol. 66, 269-276 (2010). Trastuzumab, a humanized antibody targeted against human epidermal receptor (HER)2, is used in combination with chemotherapy to treat patients with breast cancers overexpressing HER2. Despite initial clinical responses, disease progresses in a significant proportion of patients treated with trastuzumab and chemotherapy. Evidence of resistance to trastuzumab has not deterred a widespread clinical practice in the treatment of metastatic breast cancer - at least before lapatinib entered the clinic - which consists of continued administration of trastuzumab in combination with another chemotherapeutic drug. At present, it is not known if patients benefit from this practice. The present preclinical study demonstrates that, in the MDA-MB-361 and KPL-4 HER2(+) breast cancer models, induced resistance to trastuzumab monotherapy can be overcome by a combination of trastuzumab and granulocyte colony stimulating factor or chemotherapy. The response to trastuzumab and granulocyte colony stimulating factor appears to involve the host's immune system and antibody-dependent cellular cytotoxicity. The mechanisms underlying the response to trastuzumab and chemotherapy remain unclear.
authors.affiliation: University of California at Davis School of Medicine, Department of Public Health Sciences, Sacramento, CA, USA. huguette.albrecht@ucdmc.ucdavis.edu
authors.forename: Huguette
authors.initials: H
authors.lastname: Albrecht