title: The prognostic ease and difficulty of invasive breast carcinoma.
abstract: Breast carcinoma (BC) has been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The sheer number of reported signatures has led to speculation that everything is prognostic in BC. Here, we show that this ubiquity is an apparition caused by a poor understanding of the interrelatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological profile, or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers but who experience a distant metastasis within 5 years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intratumoral heterogeneity.
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Tofigh
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Paquet
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Livingstone
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bertos
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
authors.forename: Sadiq M
authors.initials: SM
authors.lastname: Saleh
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada.
authors.forename: Margarita
authors.initials: M
authors.lastname: Souleimanova
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Sean
authors.initials: S
authors.lastname: Cory
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Lesurf
authors.affiliation: Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Shahalizadeh
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University Health Centre, McGill University, Montreal, QC H3A 1A1, Canada.
authors.forename: Norberto
authors.initials: N
authors.lastname: Garcia Lopez
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, QC H3A 0G1, Canada.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Riazalhosseini
authors.affiliation: Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada; McGill University Health Centre, McGill University, Montreal, QC H3A 1A1, Canada.
authors.forename: Atilla
authors.initials: A
authors.lastname: Omeroglu
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, Montreal, QC H3T1E2, Canada; Department of Oncology, McGill University, Montreal, QC H2W1S6, Canada.
authors.forename: Josie
authors.initials: J
authors.lastname: Ursini-Siegel
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada; Department of Oncology, McGill University, Montreal, QC H2W1S6, Canada.
authors.forename: Morag
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H2W1S6, Canada; Institute of Community Medicine, UiT the Arctic University of Norway, Tromso 9037, Norway.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dumeaux
authors.affiliation: The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada. Electronic address: michael.t.hallett@mcgill.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D011379:Prognosis; D016019:Survival Analysis; D059467:Transcriptome