Journal Article

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

Klug, E, Mayr, D, Filipits, M, Fisch, K, Singer, C F, Brase, J C, Dietze, O, Petry, C, Greil, R, Rudas, M, Kronenwett, R, Bachner, M, Gnant, M, Luisser, I, Weber, K E, Jakesz, R, Sedivy, R, Gehrmann, M C, Dubsky, P, Schmidt, M

2013

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/67/1347 / 692/699/67/322 / 692/700/1750 / Antineoplastic Agents, Hormonal - administration & dosage / Antineoplastic Agents, Hormonal - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer Research / Cancer therapies / Cell Differentiation - physiology / Cell Growth Processes - physiology / Clinical Study / Clinical trials / Clinical Trials, Phase III as Topic / Drug Resistance / Endocrine therapy / Epidemiology / Female / Gene Expression Profiling / Gynecology / Gynecology. Andrology. Obstetrics / Hospitals / Humans / Mammary gland diseases / Medical prognosis / Medical research / Medical sciences / Metastasis / Molecular Medicine / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Neoplasm Metastasis / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - metabolism / Neoplasm Recurrence, Local - pathology / Nitriles - administration & dosage / Obstetrics / Oncology / Pathology / Patients / Prognosis / Proportional Hazards Models / Randomized Controlled Trials as Topic / Receptor, ErbB-2 - biosynthesis / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - metabolism / Receptors, Estrogen - biosynthesis / Receptors, Estrogen - genetics / Receptors, Estrogen - metabolism / Retrospective Studies / Signal Transduction / Surgery / Tamoxifen - administration & dosage / Tamoxifen - therapeutic use / Treatment Outcome / Triazoles - administration & dosage / Tumors