• Salvatore Pece, Davide Disalvatore, Daniela Tosoni, Manuela Vecchi, Stefano Confalonieri, Giovanni Bertalot, Giuseppe Viale, Marco Colleoni, Paolo Veronesi, Viviana Galimberti, and Pier Paolo Di Fiore.
• European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, 20142 Milano, Italy. Electronic address: salvatore.pece@ieo.it.
• EBioMedicine. 2019 Apr 1; 42: 352-362.

BackgroundBreast cancers show variations in the number and biological aggressiveness of cancer stem cells that correlate with their clinico-prognostic and molecular heterogeneity. Thus, prognostic stratification of breast cancers based on cancer stem cells might help guide patient management.MethodsWe derived a 20-gene stem cell signature from the transcriptional profile of normal mammary stem cells, capable of identifying breast cancers with a homogeneous profile and poor prognosis in in silico analyses. The clinical value of this signature was assessed in a prospective-retrospective cohort of 2, 453 breast cancer patients. Models for predicting individual risk of metastasis were developed from expression data of the 20 genes in patients randomly assigned to a training set, using the ridge-penalized Cox regression, and tested in an independent validation set.FindingsAnalyses revealed that the 20-gene stem cell signature provided prognostic information in Triple-Negative and Luminal breast cancer patients, independently of standard clinicopathological parameters. Through functional studies in individual tumours, we correlated the risk score assigned by the signature with the proliferative and self-renewal potential of the cancer stem cell population. By retraining the 20-gene signature in Luminal patients, we derived the risk model, StemPrintER, which predicted early and late recurrence independently of standard prognostic factors.InterpretationOur findings indicate that the 20-gene stem cell signature, by its unique ability to interrogate the biology of cancer stem cells of the primary tumour, provides a reliable estimate of metastatic risk in Triple-Negative and Luminal breast cancer patients independently of standard clinicopathological parameters.Copyright © 2019. Published by Elsevier B.V.

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