Practical Implications of Gene-expression-based Assays for Breast Oncologists

Overview

Journal Nat Rev Clin Oncol

Specialty Oncology

Date 2011 Dec 7

PMID 22143140

Citations 144

Authors

Aleix Prat

Matthew J Ellis

Charles M Perou

Affiliations

Soon will be listed here.

Abstract

Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology, and more recently on clinical care. Two statistical approaches underlie these advancements. Supervised analyses have led to the development of gene-expression signatures designed to predict survival and/or treatment response, which has resulted in the development of new clinical assays. Unsupervised analyses have identified numerous biological signatures including signatures of cell type of origin, signaling pathways, and of cellular proliferation. Included within these biological signatures are the molecular subtypes known as the 'intrinsic' subtypes of breast cancer. This classification has expanded our appreciation of the heterogeneity of breast cancer and has provided a way to sub-classify the disease in a manner that might have clinical utility. In this Review, we discuss the clinical utility of gene-expression-based assays and their technical potential as clinical tools vis-a-vis the performance of breast cancer biomarkers that are the current standard of care.

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References

Rakha E, Reis-Filho J, Baehner F, Dabbs D, Decker T, Eusebi V . Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010; 12(4):207. PMC: 2949637. DOI: 10.1186/bcr2607. View

Perez E, Suman V, Davidson N, Martino S, Kaufman P, Lingle W . HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006; 24(19):3032-8. DOI: 10.1200/JCO.2005.03.4744. View

Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham D . Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997; 89(22):1673-82. DOI: 10.1093/jnci/89.22.1673. View

Harvey J, Clark G, Osborne C, Allred D . Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999; 17(5):1474-81. DOI: 10.1200/JCO.1999.17.5.1474. View

Glas A, Floore A, Delahaye L, Witteveen A, Pover R, Bakx N . Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics. 2006; 7:278. PMC: 1636049. DOI: 10.1186/1471-2164-7-278. View

Mackay A, Weigelt B, Grigoriadis A, Kreike B, Natrajan R, AHern R . Microarray-based class discovery for molecular classification of breast cancer: analysis of interobserver agreement. J Natl Cancer Inst. 2011; 103(8):662-73. PMC: 3079850. DOI: 10.1093/jnci/djr071. View

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M . A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-26. DOI: 10.1056/NEJMoa041588. View

Bartlett J, Going J, Mallon E, Watters A, Reeves J, Stanton P . Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001; 195(4):422-8. DOI: 10.1002/path.971. View

Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J . Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006; 98(4):262-72. DOI: 10.1093/jnci/djj052. View

10.

Fan C, Oh D, Wessels L, Weigelt B, Nuyten D, Nobel A . Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006; 355(6):560-9. DOI: 10.1056/NEJMoa052933. View

11.

Tsoi D, Inoue M, Kelly C, Verma S, Pritchard K . Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer. Oncologist. 2010; 15(5):457-65. PMC: 3227972. DOI: 10.1634/theoncologist.2009-0275. View

12.

Pillai R, Deeter R, Rigl C, Nystrom J, Miller M, Buturovic L . Validation and reproducibility of a microarray-based gene expression test for tumor identification in formalin-fixed, paraffin-embedded specimens. J Mol Diagn. 2011; 13(1):48-56. PMC: 3070545. DOI: 10.1016/j.jmoldx.2010.11.001. View

13.

Turbin D, Leung S, Cheang M, Kennecke H, Montgomery K, McKinney S . Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases. Breast Cancer Res Treat. 2007; 110(3):417-26. DOI: 10.1007/s10549-007-9736-z. View

14.

Press M, Finn R, Cameron D, Di Leo A, Geyer C, Villalobos I . HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res. 2008; 14(23):7861-70. DOI: 10.1158/1078-0432.CCR-08-1056. View

15.

Alexe G, Dalgin G, Scanfeld D, Tamayo P, Mesirov J, DeLisi C . High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates. Cancer Res. 2007; 67(22):10669-76. DOI: 10.1158/0008-5472.CAN-07-0539. View

16.

Press M, Sauter G, Bernstein L, Villalobos I, Mirlacher M, Zhou J . Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res. 2005; 11(18):6598-607. DOI: 10.1158/1078-0432.CCR-05-0636. View

17.

Dybdal N, Leiberman G, Anderson S, McCune B, Bajamonde A, Cohen R . Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat. 2005; 93(1):3-11. DOI: 10.1007/s10549-004-6275-8. View

18.

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S . American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007; 25(33):5287-312. DOI: 10.1200/JCO.2007.14.2364. View

19.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron J, Nobel A . Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003; 100(14):8418-23. PMC: 166244. DOI: 10.1073/pnas.0932692100. View

20.

Jerevall P, Ma X, Li H, Salunga R, Kesty N, Erlander M . Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer. 2011; 104(11):1762-9. PMC: 3111159. DOI: 10.1038/bjc.2011.145. View