GEP Score Research Articles

Utility of Gene Expression Profiling Test (GEP) Score Instability To Predict Future Clinical Outcomes in Heart Transplant: Results from the CARGO 2 European-Based Multicenter Trial

Purpose GEP (AlloMap) score instability has been shown to predict of events of graft dysfunction or death in an analysis of the IMAGE data set by Deng et al. Our goal is to test this hypothesis in the independent CARGO 2 patient data set. Methods and Materials In a case-cohort design, patients with >2 serial GEP tests were studied in multivariate Cox regression models to predict future clinical events. Intra-patient GEP score instability was defined as the standard deviation of an individual’s cumulative test scores. GEP score (range 0-39), GEP score ≥34, and GEP score stability were studied. Results GEP scores tend to rise and become more stable in the whole population during the first year post-transplantation than after 1 year. After 12 months, GEP score instability (p=0.001) and GEP ≥34 (p=0.06) predict future events. [ figure 1 ]

466 The Combination of Left Ventricular Torsion and Global Strain Based on Two-Dimensional Speckle Tracking Echocardiography Could Detect Treatment-Requiring Rejection in Heart Transplant Recipients

detecting risk of rejection in cardiac transplant recipients. Clinical factors, other than cellular rejection, may be reflected in the results of this testing. A better understanding of these clinical factors is important in interpreting test results. We hypothesized that pre-transplant panel reactive antibody testing and racial mismatch between donor and recipient could affect GEP results. Methods and Materials: We studied 140 GEP test results performed in 52 post-cardiac transplant recipients at our center. Peripheral blood mononuclear cells were isolated and processed. Samples were subjected to Allomap® GEP testing. Some patients had a single test, and others had up to 9 tests performed at various time points. Results: The GEP test scores were evaluated using univariate and multivariate modeling. Since transplant rejection grade is known to increase GEP score, the data were stratified based on rejection grade. Current prednisone dose emerged as an independent predictor of the GEP score, consistent with previously published data. Intravenous or oral pulse steroid dosing within the previous 30 days also emerged as an independent predictor. Quantitative panel reactive antibody testing (p 0.05) and racial mismatch between the donor and recipient (p 0.05) were independent predictors of the GEP score. The age of the donor, the age of recipient, gender-mismatch between donor and recipient, and the use of cyclosporine-based immunosuppression versus tacrolimus-based immunosuppression were not independent predictors of GEP score. Conclusions: These data suggest that clinical factors affect immune activation, particularly pre-transplant panel reactive antibodies and donorrecipient differences. Furthermore, the data suggest that these effects persist on current immunosuppressant regimens and influence GEP test results. These clinical parameters should be taken into account when interpreting results of GEP testing.

Breast cancer testing strategies and the utilization of targeted therapies: Data from the real world

e17518 Background: HER2 testing and the use of trastuzumab is considered a prototype for the translation of a genomic therapy, yet almost nothing is known about use in practice. Uncertainties about the performance of the two types of HER2 tests, immunohistochemistry (IHC) and fluorescence-in-situ-hybridization (FISH) have led to debate about how best to identify women who are most likely to benefit from this costly treatment. Similarly, little is known about the use of gene expression profiling (GEP - e.g., OncotypeDx), which offers the possibility of better recurrence estimation to tailor the use of adjuvant chemotherapy. Methods: Cross-sectional record review of women, 36–64 years, with a new diagnosis of breast cancer in 2006–2007, identified using claims from a large, national health plan (n = 392 to date). Results: Almost all women had a HER2 test (97.7%): 56.2% had IHC alone, 17.4% had FISH alone, and 24.0% had both (2.4% had documentation of a test but not test type). Data for women with both IHC and FISH is shown below. Using the maximum of all available results, 24.9% were HER2-positive, 11.1% intermediate, and 63.9% HER2-negative. Only 55.2% of HER2-positive women received trastuzumab, compared to 16.7% of women with an intermediate score, and no HER2-negative women. The majority of women (85.7%) did not have GEP. Among women with GEP, 58.9% indicated low recurrence risk, 21.4% medium risk, and 5.4% high risk. Adjuvant chemotherapy was received by 27.3%, 91.7%, and 100% respectively (p < 0.001). Conclusions: HER2 tests, primarily IHC, are widely used. There are discrepancies in classification of HER2 status based on IHC vs. FISH. We did not find evidence of overuse of trastuzumab by women who were HER2-negative. Further work should clarify whether the lack of trastuzumab for HER2-positive women is clinically appropriate. We found modest adoption of GEP, and GEP score was associated with the use of adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.