A significant number of genes induced by E2 in vitro are correlated with age-corrected mRNA expression of ERα in human breast tumors. (a) Scatter plot of ERα expression versus age in ERα+ breast tumor samples from the profile data from . The dotted line is used to stratify the samples into ER/age high (above the line) and ER/age low (below the line) groups. Figure adapted from . (b) GSEA of the cluster B genes (induced early by E2 and sustained over time; Figure 1a) against the overall ranking of genes according to similarity with ERα mRNA (ESR1) expression in the cohort of ERα+ breast tumor profiles from . The ES statistic (the maximum of the ES running sum) is high if many genes in the set of interest appear near the top of the ranked list. Vertical bars along the ES plot denote occurrences of a cluster B gene. (c) GSEA of the cluster B genes against gene ranking by similarity with ESR1 expression as corrected for patient age (using dotted line in (a)). (d) GSEA results for estrogen-regulated gene clusters A to H against four different gene rankings tested. The FWER p-value corrects for multiple gene set testing. (e) Enrichment of cluster B genes within the set of genes showing positive correlation (p < 0.05) with ESR1 expression in a set of tumor profiles from patients within a narrow age range of 41 to 44 years. In the gene list: an asterisk indicates negatively correlated (p < 0.05) with age in ERα+ tumors; bold type indicates having higher expression in ERα+ compared to ERα- breast tumors (p < 0.01); and italics indicate induced by E2 in breast tumor xenografts (p < 0.05; Figure 1b).