Gene expression profile and response to trastuzumab-docetaxel-based treatment in breast carcinoma

BACKGROUND: Resistance to trastuzumab is often observed in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been shown to involve multiple potential mechanisms. We examined the ability of microarray analyses to determine the potential markers of pathological complete response (pCR). METHODS: We conducted an analysis of tumours from 38 patients with locally advanced HER2-positive breast cancer who had received trastuzumab combined with docetaxel. Quantitative reverse transcriptase (RT)-PCR was used to assess the expression of 30 key genes; microarray analyses were carried out on 25 tumours to identify a prognostic gene expression profile, with 13 blinded samples used to validate the identified profile. RESULTS: No gene was found to correlate with response by RT -PCR. The microarray analysis identified a gene expression profile of 28 genes, with 12 upregulated in the pCR group and 16 upregulated in non-pCR. The leave-one-out cross-validation test exhibited 72% accuracy, 86% specificity, and 55% sensitivity. The 28-gene expression profile classified the 13 validation samples with 92% accuracy, 89% specificity, and 100% sensitivity. CONCLUSION: Our results suggest that genes not involved in classical cancer pathways such as apoptosis or DNA repair could be involved in responses to a trastuzumab-docetaxel-based regimen. They also describe for the first time a gene expression signature that predicts trastuzumab response. British Journal of Cancer (2009) 101, 1357-1364. doi:10.1038/sj.bjc.6605310 www.bjcancer.com Published online 15 September 2009 (C) 2009 Cancer Research UK