Clinical Utility of Comprehensive Microarray Testing in Early-stage Breast Cancer

Richard A Bender, Femke A de Snoo
US Oncology & Hematology, 2011;7(2):107-10
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Abstract

Microarray gene expression profiling in the diagnostic setting offers the opportunity of reading out multiple profiles and genes from a single array. Several additional profiles have been added to the Agendia breast cancer suite called Symphony(TM), along with MammaPrint, a US Food and Drug Administration (FDA) cleared prognostic and predictive assay, by virtue of this technology. These additional profiles, TargetPrint, BluePrint, and TheraPrint, expand the clinical utility of the Symphony profile. They also demonstrate the versatility of gene expression profiling in the diagnostic setting, enabling the addition of many more clinically relevant profiles (such as drug response profiles) as experience grows.
Keywords
Breast cancer, microarray testing, estrogen receptor, molecular subtyping, luminal, basal
Disclosure Richard A Bender, MD, FACP, is an employee of Caris Life Sciences, Inc. Femke A de Snoo, MD, PhD, is an employee of Agendia BV.
Received: April 05, 2011 Accepted June 06, 2011
Correspondence: Femke A de Snoo, MD, PhD, Director, Medical Affairs, Department of Medical Affairs, Agendia BV, Science Park 406, 1098 XH Amsterdam, The Netherlands. E: Femke.desnoo@agendia.com

Early detection and treatment of breast cancer have dramatically improved patient survival and favorably influenced the natural history of the disease. Clinicopathologic criteria such as tumor size and lymph-node involvement have historically been used to guide treatment, and earlier detection has now placed more emphasis on prognostic as well as predictive biomarkers that are useful in planning treatment for patients with early stage disease (i.e. T1–2, N0–1,M0). Traditional biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are combined with genomic profiling,1,2 multiple gene or protein biomarkers,3 and molecular subtyping4,5 to improve treatment recommendations. In addition, gene expression read out for ER, PR and HER2 is offered to supplement conventional immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) testing;6 expression profiling offers the technical advantages of being both quantitative and more objective than IHC.

Three assays have emerged commercially representing three different technologies: MammaPrint (microarray), Oncotype DX (realtime polymerase chain reaction [RT-PCR]), and Mammostrat (immunohistochemistry [IHC]).1,3,7 All use differing technologies to identify and ‘quantitate’ gene (i.e. MammaPrint or Oncotype DX) or protein (i.e. Mammostrat) expression along with different algorithms to assess the risk of recurrence. Mammostrat looks at five proteins, Oncotype DX at 21 genes (16 target and five reference), and MammaPrint at 70 target genes with an additional 465 normalization and 536 control genes, whose simultaneous detection and measurement is facilitated by the scalability of the microarray platform. MammaPrint measures 70 genes found to be important in the prognosis of untreated women with early-stage breast cancer as determined by genome wide analysis. Currently, MammaPrint is the only US Food and Drug Administration (FDA) cleared prognostic and predictive assay for breast cancer. Several additional signatures have been added to the diagnostic array to enhance the clinical utility MammaPrint. These additional signatures include TargetPrint,6 which measures the quantitative expression of ER, PR and HER2; BluePrint,5 which uses an 80-gene profile to characterize the patient’s tumor as luminal, basal, or ERBB2 (HER2) type; and TheraPrint, which looks at 56 genes that are the targets of a variety of antineoplastic agents or which have been shown to be involved in resistance or response.

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