Gene Expression Profiles Discriminate between Pathological Complete Response and Resistance to Neoadjuvant FEC100 in Breast Cancer

Cancer Genomics Proteomics. 2006 Mar-Apr;3(2):89-95. Epub 2006 Mar 1.

Abstract

Background: In breast cancer treatment, FEC100 (fluorouracil, epirubicin and cyclophosphamide) chemotherapy delivered in a neoadjuvant setting is still applied empirically to all patients. The aim of this study was to establish a multigene classifier of sensitivity to neoadjuvant FEC100.

Materials and methods: cDNA nylon microarrays, containing 15,000 genes, were used to analyze the gene expression profiles of tumour biopsies collected before chemotherapy: 8 were typed as pathological complete responders and 8 as non-responders according to their histological and clinical responses.

Results: A classifier was generated by means of Linear Discriminant Analysis and was evaluated by leave-one-out cross-validation. The difference of expression of the NDUFB5 gene (NADH dehydrogenase 1 beta subcomplex, 5), the best discriminating gene, was verified using RT-PCR.

Conclusion: This preliminary work requires further investigations, especially in terms of larger cohorts, before the results can be transferred to clinical practice.

Keywords: Neoadjuvant fluorouracil; breast cancer; drug resistance; epirubicin and cyclophosphamide chemotherapy; gene expression profiles.