Multigene Predictors in Early-stage Breast Cancer: Moving in or Moving out?

Jeffrey S Ross


Expert Rev Mol Diagn. 2008;8(2):129-135. 

In This Article

Other Microarray-based Multigene Predictors

The Rotterdam Signature, also known as the 76-gene assay, was developed at the Erasmus University Cancer Center in Rotterdam, The Netherlands, and is being commercially developed by the Veridex Corp. (Veridex LLC, Warren, NJ, USA). Sharing no genes in common with either Oncotype Dx or MammaPrint, this stand-alone prognostic test is validated for lymph node-negative patients independent of hormone receptor status.[22,23] The gene list for this assay is heavily weighted towards proliferation genes. This assay requires fresh/frozen extracted mRNA and, similar to MammaPrint, has not been validated for use on FFPE tissues or core biopsies. The Invasiveness Signature (OncoMed Pharmaceuticals, Redwood City, CA, USA) consists of 186 genes and is designed for both node-negative and -positive and ER-negative and -positive breast cancers and also appears to predict prognosis for lung and prostate cancers as well as medulloblastoma.[24] The NuvoSelect (Nuvera Bioscience, Inc., Woburn, MA, USA) assay uses a 30-gene set to predict complete response to preoperative paclitaxel (Taxol®), 5-fluouracil, doxorubicin (Adriamycin) and cyclophosphamide (TFAC) chemotherapy and a 200-gene set to predict tumor response after 5 years of endocrine therapy.[25,26] This program also identified the overexpression of mRNA of the biomarker microtubule-associated protein (MAP)-tau as a major predictor of resistance to the TFAC regimen but at the same time a predictor of increased sensitivity to endocrine therapy among the ER-positive patients.[27]

Another microarray-based test for breast cancer is the CytoChrome p450 CYP2D6 Genotyping Test (Roche Diagnostics Inc., Indianapolis, IN, USA). Evidence suggests that, for patients deficient in CYP2D6 who have been diagnosed with ER-positive breast cancers, aromatase inhibitors may be the preferred hormonal therapeutics rather than tamoxifen.[28,29,30] This assay has been approved by the FDA and, recently, the Laboratory Corporation of America (LCA; Burlington, NC, USA) has announced a partnership with Medco Health Solutions (Medco Health Solutions Inc., Franklin Lakes, NJ, USA), designed to offer CYP2D6 testing on a large scale. A number of smaller laboratories have announced the availability of homebrew assays for this biomarker. It is too early to know whether this approach towards personalizing the selection of hormonal therapy will become widely used.


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