Gene Expression Profiling for Therapy Prediction in a Breast Cancer Neoadjuvant Therapy Study Applying Docetaxel/Epirubicin/Cyclophosphamide.

Abstract

Abstract Background: Gene expression profiling is a powerful tool to identify markers associated with clinical and therapy outcome of cancer patients. Prediction of the response to neoadjuvant regimens remains a persistent challenge. Aim of this ongoing study is the development of a gene set predicting the response of the tumor to a taxane- anthracycline based neoadjuvant chemotherapy.Material and Methods: Microarray expression profiling was performed on biopsy samples from patients before treatment using Human Genome Survey microarrays (HGSM). The protocol for a phase II study was elaborated for the treatment of breast cancer patients suffering from a primary tumor 1.5 cm or inflammatory breast cancer with Docetaxel/Epirubicin/Cyclophosphamide (TEC) prior to surgical treatment. The study was approved by the local ethical committee and all patients signed an informed consent.Results: Overall 80 patients have been enrolled in the presented study. High quality gene expression data were available from 58 patients. Of these patients 21 responded to the TEC regimen (pCR or MIB1 expressing cells in the residual tumor <= 5% and decrease of Mib1-expression >= 20%). Based on the gene-expression profile we were able to identify a preliminary gene set of 150 genes which allows us to separate responding tumors from the non responding ones based on their gene expression profile. A comparable separation of the groups could not achieved by established tumor markers, e.g. ER, PgR, HER2, uPA etc. which are measured simultaneously on the HGSM. Among the genes distinguishing the two groups several genes normally expressed in mononuclear blood cells were identified, pointing to the presence of tumor infiltrating leukocytes, predominantly in the tumors responding the TEC regimen. The presence of these cells has already been verified in a subset of the samples.Conclusion: We identified a gene set which allows to select patients who will benefit from neoadjuvant chemotherapy. Furthermore at least in the so far investigated samples tumor infiltrating leukocytes are significantly more often found in tumors which respond to a taxane- anthracycline based neoadjuvant chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2039.