Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy

Richard Buus, Ivana Sestak, Ralf Kronenwett, Carsten Denkert, Peter Dubsky, Kristin Krappmann, Marsel Scheer, Christoph Petry, Jack Cuzick, Mitch Dowsett, Richard Buus, Ivana Sestak, Ralf Kronenwett, Carsten Denkert, Peter Dubsky, Kristin Krappmann, Marsel Scheer, Christoph Petry, Jack Cuzick, Mitch Dowsett

Abstract

Background: Estimating distant recurrence (DR) risk among women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer helps decisions on using adjuvant chemotherapy. The 21-gene Oncotype DX recurrence score (RS) is widely used for this. EndoPredict (EPclin) is an alternative test combining prognostic information from an eight-gene signature (EP score) with tumor size and nodal status. We compared the prognostic information provided by RS and EPclin for 10-year DR risk.

Methods: We used likelihood ratio χ² and Kaplan-Meier survival analyses to compare prognostic information provided by EP, EPclin, RS, and the clinical treatment score (CTS) of clinicopathologic parameters in 928 patients with ER+ disease treated with five years' anastrozole or tamoxifen. Comparisons were made for early (0-5 years) and late (5-10 years) DR according to nodal status. All statistical tests were two-sided.

Results: In the overall population, EP and EPclin provided substantially more prognostic information than RS (LRχ(2): EP = 49.3; LRχ(2): EPclin = 139.3; LRχ(2): RS = 29.1), with greater differences in late DR and in node-positive patients. EP and EPclin remained statistically significantly prognostic when adjusted for RS (ΔLRχ(2): EP+RS vs RS = 20.2; ΔLRχ(2): EPclin+RS vs RS = 113.8). Using predefined cut-offs, EPclin and RS identified 58.8% and 61.7% patients as low risk, with hazard ratios for non-low vs low risk of 5.99 (95% confidence interval [CI] = 3.94 to 9.11) and 2.73 (95% CI = 1.91 to 3.89), respectively.

Conclusions: EP and EPclin were highly prognostic for DR in endocrine-treated patients with ER+, HER2-negative disease. EPclin provided more prognostic information than RS. This was partly but not entirely because of EPclin integrating molecular data with nodal status and tumor size.

© The Author 2016. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
CONSORT diagram of the availability of samples for analysis from the Arimidex, Tamoxifen, Alone or in Combination trial. ATAC = Arimidex, Tamoxifen, Alone or in Combination; ER = estrogen receptor; PgR = progesterone receptor.
Figure 2.
Figure 2.
Kaplan-Meier estimates for 10-year distant recurrence according to EP, EPclin, and recurrence score, split into tertiles in all patients. Kaplan-Meier curves were calculated and tested for equality using the log-rank test. The numbers of patients at risk in each group at various time points are given below each graph. All statistical tests were two-sided. CI = confidence interval; EP = EndoPredict; HR = hazard ratio; RS = recurrence score.
Figure 3.
Figure 3.
Kaplan-Meier plots for 10-year distant recurrence according to EP, EPclin, and recurrence score in all patients, stratified by cut-offs used for clinical decision-making. Kaplan-Meier curves were calculated and tested for equality using the log-rank test. The numbers of patients at risk in each group at various time points are given below each graph. All statistical tests were two-sided. CI = confidence interval; EP = EndoPredict; HR = hazard ratio; RS = recurrence score.
Figure 4.
Figure 4.
Kaplan-Meier plot of risk groups classified by EPclin and recurrence score for 10-year distant recurrence in all patients. Kaplan-Meier curves were calculated and tested for equality using the log-rank test. The numbers of patients at risk in each group at various time points are given below each graph. All statistical tests were two-sided. CI = confidence interval; EP = EndoPredict; HR = hazard ratio; RS = recurrence score.

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Source: PubMed

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