Commercialized Multigene Predictors of Clinical Outcome for Breast Cancer

Abstract

Learning Objectives: After completing this course, the reader will be able to: Assess the strengths and weaknesses of the four main techniques used to measure multiple gene expression using clinical breast cancer specimens.Compare the advantages and disadvantages of the oncotype DX™ and MammaPrint® multigene assays and compare the TAILORx and MINDACT clinical trials for the prediction of clinical outcome in breast cancer.Evaluate the costs versus benefits associated with the use of expensive multigene breast cancer predictors in the management of breast cancer. CME This article is available for continuing medical education credit at CME.TheOncologist.com In the past 5 years, a number of commercialized multigene prognostic and predictive tests have entered the complex and expanding landscape of breast cancer companion diagnostics. These tests have used a variety of formats ranging from the familiar slide-based assays of immunohistochemistry and fluorescence in situ hybridization to the nonmorphology-driven molecular platforms of quantitative multiplex real-time polymerase chain reaction and genomic microarray profiling. In this review, 14 multigene assays are evaluated as to their scientific validation, current clinical utility, regulatory approval status, and estimated cost–benefit ratio. Emphasis is placed on two tests: oncotype DX™ and MammaPrint®. Current evidence indicates that the oncotype DX™ test has the advantages of earlier commercial launch, wide acceptance for payment by third-party payors in the U.S., ease of use of formalin-fixed paraffin-embedded tissues, recent listing by the American Society of Clinical Oncology Breast Cancer Tumor Markers Update Committee as recommended for use, continuous scoring system algorithm, ability to serve as both a prognostic test and predictive test for certain hormonal and chemotherapeutic agents, demonstrated cost-effectiveness in one published study, and a high accrual rate for the prospective validation clinical trial (Trial Assigning Individualized Options for Treatment). The MammaPrint® assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node–positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). A number of other assays have specific predictive goals that are most often focused on the efficacy of tamoxifen in ER-positive patients, such as the two-gene ratio test and the cytochrome P450 CYP2D6 genotyping assay.