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.