Abstract
PURPOSE: Few studies have compared the performance of gene-expression profiling tests (e.g. Oncotype-Dx) to clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS5) or tools that combine both (e.g. RSClin) in patients with early breast cancer (EBC). A large trial dataset was used to evaluate the prognostic performance of different tests based on patient outcomes. METHODS: The TEAM pathology cohort accrued samples from 4736 postmenopausal hormone positive women with EBC, treated with either exemestane or tamoxifen followed by exemestane. Oncotype-Dx-trained risk scores were previously generated by gene-expression profiling. Patient data was used to calculate various recurrence scores. Analysis was restricted to the N0/N1 population and prognostic ability of selected risk tools was assessed using Cox regression analysis and Harrell's C-statistic. RESULTS: Results were available for 2065 patients. There was low correlation between PREDICT 2.1 (r = -0.12), INFLUENCE 2.0 (r = 0.20), CTS5 (r = 0.16) with Oncotype-Dx-trained results. In N0 patients, RSClin had improved prognostic ability (C-statistic = 0.66) on DMFS compared to PREDICT 2.1 (0.60), INFLUENCE 2.0 (0.57), CTS-5 (0.62), and Oncotype-Dx (0.63). CONCLUSION: Combining molecular and clinico-pathologic factors enhances prognostic information. However, the impact of this on actual patient management requires further prospective validation. The trial is registered with clinicaltrials.gov NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001.