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. 2020 Aug 11;22:85. doi: 10.1186/s13058-020-01324-4

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — A novel gene signature of HER2 activity incorporating ERBB2mut, ERBB2 amplification, and clinical HER2 status. a Generation of a 20-gene signature of HER2 activity. The upper Venn diagrams show the overlap between the top 500 DEGs by WAD score for METABRIC amplified vs. non-amplified, ERBB2 mutant vs. wild-type, and TCGA HER2+ vs. HER2−. Upregulated DEGs are shaded blue and down-regulated DEGs yellow. ERBB2mut and oncERBB2mut vs. wild-type are analyzed separately, and the overlap combined in the lower Venn diagrams. b Comparison with an established 24-gene signature of HER pathway activation [31], using a gene signature (genesig) score derived from multivariate analysis of response to neratinib in breast cancer cell lines. Cases with ERBB2mut (gray lines) and oncERBB2mut (blue lines) clustered in the upper quartile of normalized genesig scores for the novel signature but not the established signature. c 10-year OS analysis of cases in the current study stratified by histological subtype and novel genesig score (upper vs. lower quartiles) indicates that ERBB2mut-associated DEGs are prognostic in ILC but not IDC. GE, geneset enrichment