Commercialized multigene predictors of clinical outcome for breast cancer.
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.
Ross
Jeffrey S
JS
Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York 12208, USA. rossj@mail.amc.edu
Hatzis
Christos
C
Symmans
W Fraser
WF
Pusztai
Lajos
L
Hortobágyi
Gabriel N
GN
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000191:economics / Q000235:genetics*; D003362:Cost-Benefit Analysis; D018795:Device Approval; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000592:standards; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014481:United States; D014486:United States Food and Drug Administration
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen