Next-generation Sequencing

A Powerful Tool for the Discovery of Molecular Markers in Breast Ductal Carcinoma In Situ

Hitchintan Kaur; Shihong Mao; Seema Shah; David H Gorski; Stephen A Krawetz; Bonnie F Sloane; Raymond R Mattingly


Expert Rev Mol Diagn. 2013;13(2):151-165. 

In This Article

Transcriptome Profiling by Microarrays

Microarrays have been the technology of choice for most gene expression studies and have been extensively used for studying invasive breast cancer, with results being adapted for clinical use. This approach has also been used to advance the understanding of premalignant breast disease. Microarrays provide gene expression information in a high-throughput manner and thus afford opportunities to identify the unique transcriptional fingerprint associated with each stage of disease progression.

Two microarray-derived tests for breast cancer are commercially available. MammaprintTM is a 70-gene predictor for breast cancer outcome.[108] The Oncotype DX® assay[109] utilizes expression analysis of 21 genes for risk stratification and prognosis of breast cancer patients. These examples reflect the potential of microarrays to identify biomarkers of disease for screening patients. Two long-term, large-scale randomized trials (TAILORx and MINDACT) are underway to determine the clinical utility of Oncotype DX and Mammaprint. Validation of novel biomarkers is essential before their application in routine clinical use and treatment-related decisions. This is exemplified by the fact that two clinical trials in non-small-cell lung cancer and one trial in breast cancer, which were based on genomic signatures thought to predict the outcome of chemotherapy, had to be terminated in 2011 due to insufficient prior validation.[110,111]