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Cell Rep. 2014 Oct 9;9(1):129-142. doi: 10.1016/j.celrep.2014.08.073. Epub 2014 Oct 2.

The prognostic ease and difficulty of invasive breast carcinoma.

Author information

1
The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada; Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
2
The Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A1A3, Canada.
3
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.
4
Centre for Bioinformatics, McGill University, Montreal, QC H3G0B1, Canada.
5
Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University Health Centre, McGill University, Montreal, QC H3A 1A1, Canada.
6
Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University and Génome Québec Innovation Centre, Montreal, QC H3A 0G1, Canada.
7
Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada; McGill University Health Centre, McGill University, Montreal, QC H3A 1A1, Canada.
8
Lady Davis Institute for Medical Research, McGill University, Montreal, QC H3T1E2, Canada; Department of Oncology, McGill University, Montreal, QC H2W1S6, Canada.
9
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.
10
Department of Oncology, McGill University, Montreal, QC H2W1S6, Canada; Institute of Community Medicine, UiT the Arctic University of Norway, Tromso 9037, Norway.
11
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.

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.

PMID:
25284793
DOI:
10.1016/j.celrep.2014.08.073
[Indexed for MEDLINE]
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