Tumour type (IMC=invasive mammary carcinoma, IDC=invasive ductal carcinoma)

Baylor College of Medicine, Houston, TX, USA

Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer

BACKGROUND: Systemic chemotherapy for operable breast cancer substantially
decreases the risk of death. Patients often have de novo resistance or incomplete
response to docetaxel, one of the most active agents in this disease. We
postulated that gene expression profiles of the primary breast cancer can predict
the response to docetaxel. METHODS: We took core biopsy samples from primary
breast tumours in 24 patients before treatment and then assessed tumour response 
to neoadjuvant docetaxel (four cycles, 100 mg/m2 daily for 3 weeks) by cDNA
analysis of RNA extracted from biopsy samples using HgU95-Av2 GeneChip. FINDINGS:
From the core biopsy samples, we extracted sufficient total RNA (3-6 microg) for 
cDNA array analysis using HgU95-Av2 GeneChip. Differential patterns of expression
of 92 genes correlated with docetaxel response (p=0.001). Sensitive tumours had
higher expression of genes involved in cell cycle, cytoskeleton, adhesion,
protein transport, protein modification, transcription, and stress or apoptosis; 
whereas resistant tumours showed increased expression of some transcriptional and
signal transduction genes. In leave-one-out cross-validation analysis, ten of 11 
sensitive tumours (90% specificity) and 11 of 13 resistant tumours (85%
sensitivity) were correctly classified, with an accuracy of 88%. This 92-gene
predictor had positive and negative predictive values of 92% and 83%,
respectively. Correlation between RNA expression measured by the arrays and
semiquantitative RT-PCR was also ascertained, and our results were validated in
an independent set of six patients. INTERPRETATION: If validated, these molecular
profiles could allow development of a clinical test for docetaxel sensitivity,
thus reducing unnecessary treatment for women with breast cancer.