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

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.

Clinical Utility of Multigene Profiling Assays in Early-Stage Breast Cancer

“…Two studies 22,23 supported the prognostic ability of EndoPredict (Tables vi and v). Based on the tumour marker utility grading system 7,8 , both studies were assessed as category B, and thus the evidence supporting the overall prognostic ability of EndoPredict is considered to be level IB ( Table v).…”

“…Based on the tumour marker utility grading system 7,8 , both studies were assessed as category B, and thus the evidence supporting the overall prognostic ability of EndoPredict is considered to be level IB ( Table v). Given that the Austrian Breast and Colorectal Cancer Study Group 8 trial supported the assay's ability to prognosticate for local recurrence 23 and that results from both the Austrian Breast and Colorectal Cancer Study Group 6 and 8 trials support the ability to prognosticate for distant recurrence 22 , there is level II evidence supporting a role for EndoPredict in prognosticating for local recurrence and level IB evidence for distant recurrence ( Table v).…”

“…Level IB evidence 7,8 indicates that withholding chemotherapy is associated with a high-risk of recurrence in the high-risk subgroups identified through Oncotype dx 2,9-12 , Prosigna 11,12,[15][16][17][18] , and EndoPredict 22,23 . Although Oncotype dx, Prosigna, and EndoPredict are supported by level IB evidence for prognosticating high risk of recurrence in a subgroup of patients, only Oncotype dx has been evaluated to determine its ability to predict a benefit from chemotherapy.…”

“…The prognostic value of Prosigna 11,15 and EndoPredict 22,23 for late recurrence is based on a multivariate statistical analysis performed retrospectively on completed prospective trials (level II evidence 7,8 ). Although a high Oncotype dx recurrence score is also associated with late recurrence, the statistical difference between early and late recurrence loses significance on multivariate analysis 12,14 .…”

General St. Gallen-2015 guidelines for the treatment of early breast cancer (adapted by the experts of the Russian Society of Breast Oncologists)

“…Тем не менее в исследовании ATAC он не являлся предиктором отдаленного рецидива после эндокринотерапии, в то время как шкала PAM-50 ROR ® и основанная на ИГХ шкала IHC4 ® являлись прогностически значимыми и после завершения 5 лет эндокринотерапии [44,45]. Кроме того, в австрий-ских исследованиях ABCSG 6 и ABCSG 8 молекулярный маркер EndoPredict ® был прогностически значимым спустя 5 лет, особенно в сочетании с клиническими факторами [46]. В 2 исследованиях было показано, что маркер Breast Cancer Index ® (BCI) был значимым в оценке прогноза раннего и позднего дистанционного (метастатического) рецидива [47] Улучшение адъювантной эндокринотерапии у пременопаузальных женщин Комбинированный анализ испытаний TEXT и SOFT показал явное преимущество применения ИА эксеместана против тамоксифена в сочетании с подавлением функции яичников, в основном с использо-ванием трипторелина [5].…”