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Fig. 1 | Breast Cancer Research

Fig. 1

From: HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors

Fig. 1

Human epidermal growth factor-2 (HER2) amplification in breast cancer is an event on top of a luminal (Lum), basal or androgen receptor (AR)-driven state. a, b HER2 expression versus the number of ploidy-corrected HER2 copies. Tumors are colored by prediction analysis of microarray 50 (PAM50) subtype. a Among The Cancer Genome Atlas (TCGA) breast tumors, 12.3% (n = 106) are HER2 amplified (HER2A), of which 83 have high HER2 expression (defined as log2(nRPKM + 1) ≥8.2 as per Additional file 3A). nRPKM reads per kilobase of exon model per million mapped reads normalized by size factor. b Among Metabric tumors, 12% (133/1107) are HER2A, of which 120 overexpress HER2 (defined as log2 expression ratio ≥12.5 as per Additional file 3E). c For the USO1062 trial with unavailable tumor ploidy, HER2A was defined as ≥5 copies of HER: 8% (79/987) of USO1062 tumors are HER2A, of which 58 overexpress HER2 (defined as normalized log10 counts ≥1.02 as per Additional file 3G). d AR-ness score across PAM50 subtypes for 178 breast tumors from TCGA that are estrogen receptor (ER)- by immunohistochemical staining (IHC). AR-ness score is calculated as the difference in average z-scored expression of 14 positive signature genes and average z-scored expression of 31 negative signature genes. Tumors are colored by HER2A status. e AR-ness score across the integrated clusters (IntClusts) for 202 breast tumors from Metabric that are ER- by IHC. Tumors are colored by PAM50 subtype. IntClust4 is divided into IntClusts 4- and 4+ by ER IHC, as per a previous publication [3]. f Kaplan-Meier curve of overall survival (OS) in 761 TCGA tumors with a median follow up of 27 months, divided into five groups based on ER IHC status, PAM50 subtype, and AR activity (positive versus negative AR-ness score). OS was truncated to 12 years of follow up. g Left, Kaplan-Meier curve of OS in 31 ER- HER2A tumors from TCGA, divided by AR-ness score. Right, Kaplan-Meier curve of OS in 131 ER- non-HER2A tumors from TCGA, divided by AR-ness score. OS was truncated to 12 years of follow up. HER2E HER2-enriched

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