title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery and Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Dubsky
authors.forename: J C
authors.initials: JC
authors.lastname: Brase
authors.forename: R
authors.initials: R
authors.lastname: Jakesz
authors.forename: M
authors.initials: M
authors.lastname: Rudas
authors.forename: C F
authors.initials: CF
authors.lastname: Singer
authors.forename: R
authors.initials: R
authors.lastname: Greil
authors.forename: O
authors.initials: O
authors.lastname: Dietze
authors.forename: I
authors.initials: I
authors.lastname: Luisser
authors.forename: E
authors.initials: E
authors.lastname: Klug
authors.forename: R
authors.initials: R
authors.lastname: Sedivy
authors.forename: M
authors.initials: M
authors.lastname: Bachner
authors.forename: D
authors.initials: D
authors.lastname: Mayr
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: M C
authors.initials: MC
authors.lastname: Gehrmann
authors.forename: C
authors.initials: C
authors.lastname: Petry
authors.forename: K E
authors.initials: KE
authors.lastname: Weber
authors.forename: K
authors.initials: K
authors.lastname: Fisch
authors.forename: R
authors.initials: R
authors.lastname: Kronenwett
authors.forename: M
authors.initials: M
authors.lastname: Gnant
authors.forename: M
authors.initials: M
authors.lastname: Filipits
mesh_terms: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; D014230:Triazoles; C508053:ERBB2 protein, human