title: Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score.
abstract: OBJECTIVE
  We have previously shown that the PAM50-based risk of recurrence (ROR) score is significantly correlated with distant recurrence in both the translational research cohort within the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial (TransATAC) and Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) randomized trials. Here, we focus on the ROR score for predicting distant recurrence after 5 years of follow-up in a combined analysis of these two randomized trials.
  
  
  METHODS
  Long-term follow-up data and tissue samples were obtained from 2,137 postmenopausal women with hormone receptor-positive early-stage breast cancer from the ABCSG 8 and TransATAC trials. We used Cox proportional hazard regression models to determine the prognostic value of ROR for distant recurrence beyond 5 years in the combined data set.
  
  
  RESULTS
  A total of 2,137 women who did not have a recurrence 5 years after diagnosis were included in the combined analyses. The Clinical Treatment Score (CTS) was the strongest prognostic factor 5 years after diagnosis (univariable: likelihood ratio [LR] χ(2) = 94.12, bivariable: LR χ(2) = 61.43). The ROR score was significantly prognostic by itself in years 5 to 10. In the node-negative/human epidermal growth factor receptor 2-negative subgroup, more prognostic value for late distant recurrence was added by the ROR score compared with the CTS.
  
  
  CONCLUSIONS
  The ROR score added clinically meaningful prognostic information to the CTS in all patients and all subgroups in the late follow-up period. These results suggest that the ROR score may be helpful for separating patients into risk groups who could be spared or potentially benefit from extended hormonal therapy beyond 5 years of treatment.
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA. i.sestak@qmul.ac.uk.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Knowles
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Peter
authors.initials: P
authors.lastname: Dubsky
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: John Wayne
authors.initials: JW
authors.lastname: Cowens
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Sean
authors.initials: S
authors.lastname: Ferree
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Carl
authors.initials: C
authors.lastname: Schaper
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Christian
authors.initials: C
authors.lastname: Fesl
authors.affiliation: Ivana Sestak, Jack Cuzick, Queen Mary University; Mitch Dowsett, Elena Lopez-Knowles, Royal Marsden Hospital, London, United Kingdom; Martin Filipits, Peter Dubsky, Michael Gnant, Medical University of Vienna; Christian Fesl, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria; John Wayne Cowens, Sean Ferree, NanoString Technologies, Seattle, WA; and Carl Shaper, MyRAQA, Redwood Shores, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008875:Middle Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D003627:Data Interpretation, Statistical; D005500:Follow-Up Studies; D006728:Hormones / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012306:Risk; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage; D001317:Austria
chemical_list: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal; D006728:Hormones; D009570:Nitriles; D013629:Tamoxifen; D014230:Triazoles