Details

Autor(en) / Beteiligte

• Yang, Sherry X
• Dancey, Janet E
• Yang, Sherry X.
• Dancey, Janet E.

Titel

The 21-Gene Recurrence Score and Benefit of Chemotherapy in Estrogen Receptor-Positive Breast Cancer

Ist Teil von

• Handbook of Therapeutic Biomarkers in Cancer, 2013, p.387-404

Ort / Verlag

United Kingdom: Pan Stanford

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Genomics is defined as the study of all of the nucleotide sequences in an organism. “Genomic profiling” in breast cancer and other cancers has focused on the evaluation of gene expression, or the translation of the information encoded in genomic DNA into an RNA transcript. Although RNA transcripts include messenger RNAs which are translated into proteins and various other RNAs (e.g., transfer RNA, ribosomal RNA, micro RNA, and noncoding RNA) that have important biologic functions, most studies of gene expression profiling in breast cancer have focused on mRNA expression. The same principles may be applied to the study of the epigenome,4,5 microRNAs,6proteins,7 or integrative approaches that evaluate combinations of profiling methods.8 In addition, high-throughput massively parallel sequencing is now feasible, allowing direct sequencing of cDNAs which may provide not only absolute gene expression levels, but also information on alternatively spliced isoforms, mutations and novel transcripts arising from fusion genes. 13.3 Development and Validation of Multiparameter AssaysThe promise and pitfalls in developing multiparameter assays has been reviewed elsewhere,9-12 specific criteria have been proposed for the level of evidence required to define and support their clinical utility.13 There are several steps in the development of a marker, which may broadly classified as (1) conceptualization, (2) clinical development, (3) technical development, (4) validation, and (5) application. Development of an accurate assay is largely a function of the interplay between sample size and classification difficulty.14 Criteria have been developed for assessing and reporting multiparameter assays (and other tumor markers) called the REMARK guidelines (REporting recommendations for tumor MARKer prognostic studies).15 Most peer-reviewed journals require that reports describing tumor markers, including multiparameter assays, follow the REMARK guidelines in order to be considered for publication. In addition, standards termed “minimal information about a microarray experiment” (MIAME) for reporting the data have been established by the Microarray Gene Expression Data Society,16 and most journal require that the gene expression data described in the publication be deposited in a publicly available data base (e.g., Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo). Approval of multiparameter breast cancer assays is regulated under the under the provisions of the Clinical Laboratory Improvement Act of 1988 (CLIA), which applies to laboratories that examine human specimens for the diagnosis, prevention, or treatment of any disease or assessment of health. The US Food and Drug Administration issued guidance document in 2007 indicating that multiparameter assays also fall under regulatory jurisdiction of the agency under regulations governing approval of medical devices (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm079163.htm#1). A gene expression profiling test system for breast cancer prognosis was defined as a device that measures the RNA expression level of multiple genes and combines this information to yield a signature (pattern or classifier or index) to aid in prognosis. Approval provided by this mechanism is commonly known as “510(k)” clearance. Several multiparameter assays have now been approved for breast cancer by CLIA or FDA in the United States and Europe, and their characteristics are summarized in Table 13.1, including the 21-gene Recurrence Score. 13.4 Development of the 21-Gene Recurrence ScoreThe genes included in the Oncotype DX assay and algorithm used to calculate the Recurrence Score (RS) are summarized in Table 13.2. There were several critical steps in the development of this assay, including: (1) development of methodologies to extract RNA from formalin fixed paraffin embedded tissue (FFPE), to perform quantitative reverse-transcriptase-polymerase-chain-reaction Ta bl e 13 .1 Mul tiparam eteras saysfo rbreas tcance rappro vedby regulat oryage ncies A ss ay ( co m p an y) M et h od T is su e ty p e A p p ro va l P at ie n t p op u la ti on P ro gn os is /p re d ic ti on Mamm aprint 70-Gen eAssay (Agend ia) DNAMicroa rray Fresho r Frozen Europe andUS (FDA) E R -P os /N eg s ta ge III breast cancer P ro gn os ti c fo r di st an tr ec ur re nc e Oncoty peDX 21-Gen eAssay (Genom icHeal th) qR TP CR FF P E Europe andUS (CLIA) E R -P os s ta ge I- II breast cancer P ro gn os ti c fo r di st an tr ec ur re nc e P re di ct iv e of c he m ot he ra py b en ef it ifRShi gh Theros H/ISM 2-Gene Ratio (Biothe ranosti cs) qR TP CR FF P E US(CL IA) E R -P os ,L ym ph n od e Negativ eBreas t Cancer P ro gn os ti c fo r di st an tr ec ur re nc e Theros MGISM 5-Gene Molecu lar Grade qR T- P CR FF P E US(CL IA) ER-pos ,Grade 2 tumors P ro gn os is – r ec la ss if ic at io n of tumors fromg rade2 tograd e1 or3 (qRT-PCR) using RNA derived from FFPE, and to reduce sources of preanalytic and analytic variability, (2) identification of genes associated with recurrence and response to therapy in training set populations, (3) selection of the genes and development of algorithm for the RS and (4) prospective validation of the algorithm. Since the requirement for fresh or snap-frozen tissue had limited the clinical application of other arrays, methods were developed to extract RNA from FFPE and perform qRT-PCR using this material.17