The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients

P Dubsky, J C Brase, R Jakesz, M Rudas, C F Singer, R Greil, O Dietze, I Luisser, E Klug, R Sedivy, M Bachner, D Mayr, M Schmidt, M C Gehrmann, C Petry, K E Weber, K Fisch, R Kronenwett, M Gnant, M Filipits, Austrian Breast and Colorectal Cancer Study Group (ABCSG), P Dubsky, J C Brase, R Jakesz, M Rudas, C F Singer, R Greil, O Dietze, I Luisser, E Klug, R Sedivy, M Bachner, D Mayr, M Schmidt, M C Gehrmann, C Petry, K E Weber, K Fisch, R Kronenwett, M Gnant, M Filipits, Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Abstract

Background: ER+/HER2- breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy.

Methods: A total of 1702 postmenopausal ER+/HER2- breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis).

Results: EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up.

Conclusion: The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome.

Figures

Figure 1
Figure 1
Kaplan–Meier plots. Kaplan–Meier plots of distant recurrence by the EP groups between (A) 0–5 years of follow-up and (B) 5–10 years of follow-up in the combined ER+/HER2− cohort (ABCSG6/8, n=1702). Cutoff point for EP was prespecified at 5. The numbers in parentheses indicate the 95% CI of the HR.
Figure 2
Figure 2
C-indices demonstrating the prognostic performance of different clinical and molecular parameters in 1702 ER+/HER2− breast cancer patients (ABCSG6/8) after 5 years of follow-up. The values on the x axis are unbiased estimates of the c-index of the linear combination of one or more variables by Cox regression. Statistical tests indicate whether the c-index increases significantly by addition of EP to a fixed set of clinico-pathological variables. Abbreviations: EP, EndoPredict (continuous); ER, oestrogen receptor (categorical); G, grade (categorical); N, nodal status (categorical); T, tumour size (categorical).
Figure 3
Figure 3
Kaplan–Meier plots. Kaplan–Meier plot of distant recurrence by EPclin groups between (A) 0–5 years of follow-up and (B) 5–10 years of follow-up in the combined ER+/HER2− cohort (ABCSG6/8, n=1702). Cutoff point for EPclin was prespecified at 3.3. The numbers in parentheses indicate the 95% CI of the HR.

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