The Ottawa Hospital, Ottawa, ON, Canada
Ana-Alicia Beltran-Bless , Gregory Russell Pond , Jane Bayani , Sarah Barker , Melanie Spears , Elizabeth Mallon , Karen J Taylor , Annette Hasenburg , Christos Markopoulos , Luc Yves Dirix , Caroline M. Seynaeve , Cornelis J.H. Van De Velde , Daniel William Rea , Lisa Vandermeer , John Frederick Hilton , John Bartlett , Mark J. Clemons
Background: Gene-expression profiling tests (e.g. Oncotype, Mammaprint, Prosignia, Breast Cancer Index and EndoPredict) are widely used in the care of patients with early-stage hormone positive breast cancer (node negative or 1-3 lymph nodes). However, these tests are resource intensive, and few studies have compared their value with either free and widely available clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS-5) or tools that combine genomic testing with clinico-pathologic data (e.g. RSClin). The TEAM pathology substudy population was used to compare these different predicted model scores with outcomes. Methods: The TEAM pathology study consists of 3284 postmenopausal hormone positive breast cancer patients treated with either exemestane or tamoxifen followed by exemestane. Accrual was from 2001 to 2006. Genes comprising the multi-parametric Oncotype Dx were used to train signatures to create true assay results. Patient data was then used to calculate recurrence scores through various tools. This included clinico-pathologic models and their respective endpoints PREDICT 2.1 (overall survival at 5 years), INFLUENCE 2.0 (distant metastasis at 5 years), CTS-5 (distant recurrence risk at year 5-10), the purely genomic Oncotype Dx trained results (distant recurrence risk at 9 years), as well as the new clinico-pathologic RSClin (distant recurrence risk at 10 years). We compared the level of association between these predictive model scores using Spearman correlation coefficients. The prognostic ability of each model was contrasted for each outcome using Harrell’s C-statistic. Results: Results were available for CTS-5 (3022 patients), INFLUENCE 2.0 (3485 patients), ODx-trained (3825 patients), and RSClin (3029 patients). Correlation coefficients showed low correlation between Influence (r= 0.25) and CTS-5 (r= 0.17) with Oncotype-Dx trained results, and high correlation between RSClin (r = 0.84) and Oncotype-Dx trained results. The concordance index was similar (0.65 to 0.68) for all models with distant metastasis-free survival as the outcome. Analysis is ongoing and further results will be available at the time of presentation. Conclusions: Other clinico-pathologic tools such as Influence 2.0 and CTS-5 have good prognostic ability when compared to Oncotype Dx-trained results and RSClin.
ρ n | Influence | RS Clin Scores | CTS5 |
---|---|---|---|
Oncotype Scores | 0.25 3485 | 0.84 3029 | 0.17 3022 |
Influence | - | 0.56 2913 | 0.82 2913 |
RS Clin Scores | - | - | 0.53 3022 |
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