Chips to Bedside: Incorporation of Microarray Data into Clinical Practice

Abstract

Advances in analytic technologies have often driven progress in medicine. This is particularly true for diagnostics in which new imaging methods and novel molecular analytic tools such as DNA sequencing and PCR have all found their diagnostic niche and are now routinely used in the clinic. Highthroughput microarray-based analytic methods were first described over a decade ago (1). It enabled researchers to simultaneously and semiquantitatively measure the expression of thousands of mRNA species from a biological specimen in a single experiment. Molecular biologists and clinical investigators quickly realized the potential of this technology (2). It was expected that new insights into cell biology would be gained through unbiased analysis of the transcriptome, and that combinations of genes would provide more accurate prognostic and predictive tests than any single gene alone. It may be timely to reflect on what has materialized from these initial hopes, keeping in mind that it often takes several decades for a new technology to mature and show its full effect on science or show its value in clinical medicine.

High estrogen receptor expression in early breast cancer: chemotherapy needed to improve RFS?

“…Recently gene expression profiles have been developed to analyze the individual recurrence risk in order to individualize adjuvant breast cancer treatment [36][37][38][39]. For example, the 21-gene panel [40] includes mainly genes involved in tumor cell proliferation and hormonal response.…”

Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

“…Even in early-stage patients treated by surgery, the risk of recurrence is high (2), and major efforts have been made to identify molecular markers that predict prognosis and response to additional therapy (3). Microarray-based gene expression profiling has successfully been used in clinical cancer research to subclassify cancer entities, to predict prognosis or response to therapy, and to identify underlying mechanisms of tumor development (4). In breast and colorectal cancer, prognostic gene expression signatures have been validated in independent patient cohorts and are now tested in prospective randomized clinical trials (5,6).…”

Hormone receptor-positive early breast cancer: controversies in the use of adjuvant chemotherapy

“…Concomitantly, prognostic gene signatures were developed in an effort to identify, analyzing the expression of a restricted group of genes, reliable indicators of clinical outcome that could be adopted in the clinical practice. Those that are currently approved for clinical use are grouped in Table 4, but several others are currently under investigation (Pusztai 2006). One common aspect of most of these signatures is that they were developed as a pure prognostic tool to distinguish between tumors with extremely good prognosis in the absence of adjuvant treatment or of adjuvant chemotherapy, from those with poor prognosis.…”

“…Results of these analyses, which are grouped in Table 5, provided evidence for the incorporation of this test in the clinical practice to identify patients at very low risk of developing distant metastases when treated with tamoxifen alone (Harris et al 2007). The percentage of patients falling into the three risk categories in published studies is summarized in Table 6 (Paik et al 2004, 2006, Habel et al 2006, Albain et al 2007, Goldstein et al 2008. Low-risk patients account for 40-56% of hormone receptor-positive patients.…”