The prognostic ease and difficulty of invasive breast carcinoma

Breast carcinoma (BC) have 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 shear 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 inter- relatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological 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 five years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intra-tumoral heterogeneity.

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Tofigh A, Suderman M, Paquet ER, Livingstone J, Bertos N, Saleh SM, Zhao H, Souleimanova M, Cory S, Lesurf R, Shahalizadeh S, Garcia Lopez N, Riazalhosseini Y, Omeroglu A, Ursini-Siegel J, Park M, Dumeaux V, Hallett M