Global transcriptional patterns in the breast tissue following treatment with control (placebo), conjugated equine estrogens (CEE), CEE + medroxyprogesterone acetate (MPA), and high-dose tibolone (Hi Tib). (a) Venn diagram showing greater numbers of genes altered by CEE + MPA compared with CEE and Hi Tib. (b) principal component analysis and (c) heatmap of differentially regulated genes showing greater overlap between Con and Hi Tib groups and the CEE + MPA and CEE groups. (d) Functional categories of significantly altered transcripts showing overrepresentation of genes involved in cancer and several related classes. mRNA profiles were determined by microarray analysis. All diagrams correspond to significantly altered transcripts with fold-change of more than 1.5 versus control group in at least one group, adjusted analysis of variance (ANOVA) P < 0.05, and quality more than 2.