Fig. 3: Biological changes after dual HER2 blockade.

a Schematic representation of the workflow to identify differences in PAM50 gene expression signatures in HER2-E tumors at baseline of the PAMELA trial between day 14 of treatment and residual tumors. b PAM50 signature expression changes between baseline, day 14 and surgery in 57 residual tumors at surgery. Each line represents a tumor sample. Increases are represented in red and decreases in green. P-values (p) were determined by two-tailed paired t-tests. c PAM50 signature scores in BT474 and SKBR3 cells untreated, treated with TKI + trastuzumab for 72 h and upon treatment discontinuation for 72 h. Each line represents a paired sample. P-values (p) were determined by two-tailed paired t-tests. d Unsupervised hierarchical clustering using the PAM50 genes across untreated BT474 cells, treated cells with combinations of TKI and trastuzumab for 72 h and cells where treatment was removed for another 72 h. The heatmap shows high (red) to low (green) expression of mRNAs in each sample. The molecular subtype call of each sample is shown.