Fig. 1: Mutation profile of advanced breast cancer determined by ctDNA sequencing.
From: Genomic profile of advanced breast cancer in circulating tumour DNA
a Mutational profile of advanced breast cancer determined by ctDNA targeted sequencing of 800 patients in the plasmaMATCH trial. Displayed are mutations and indels likely to be pathogenic (“Methods”), summarised by gene for each patient. Top bar refers to total counts of pathogenic mutations per patient. Right, variant classification of the alterations within each gene. FS, frameshift; IF, in-frame. b Breast cancer subtype association of the most frequently mutated genes within patients with known phenotype (HR + HER2- N = 515, HER2+ N = 72, TNBC N = 138). Comparison with false discovery corrected two-sided Fisher’s exact tests (TP53: HR + HER2- vs HER2+ q = 0.003, HR + HER2- vs TNBC q < 0.0001, HER2 + vs TNBC q = 0.04; PIK3CA: HR + HER2- vs TNBC q < 0.0001, HER2 + vs TNBC q = 0.0008; ESR1: HR + HER2- vs HER2 + q < 0.0001, HR + HER2- vs TNBC q < 0.0001, HER2 + vs TNBC q = 0.008; GATA3: HR + HER2- vs TNBC q < 0.0001; HER2: HR + HER2- vs HER2 + q = 0.05, HER2 + vs TNBC q = 0.005). ns, not significant. c Patient mutation frequency split by breast cancer subtype, overall and likely pathogenic mutations in patients with known phenotype (HR + HER2- N = 515, HER2 + N = 72, TNBC N = 138). Data are presented as a violin plot with inlayed boxplot, where the middle line is the median, the lower and upper hinges represent the 25th and 75th centiles respectively and the whiskers extend from the hinge to the smallest and largest value, respectively, no further than 1.5 x IQR (interquartile range) from the lower or upper hinge. Data outside of these ranges are plotted individually. Comparison of likely pathogenic mutations with false discovery corrected two-sided pairwise Kruskal-Wallis test, HR + HER2- vs HER2 + q = 0.03, HR + HER2- vs TNBC q < 0.0001. d Frequency of copy number increases in ctDNA split by breast cancer subtype in patients with known phenotype (HR + HER2- N = 515, HER2 + N = 72, TNBC N = 138). Comparison with false discovery corrected Chi-squared tests (MYC q = 0.01, PIK3CA q < 0.0001, FGFR1 q = 0.01, EGFR q = 0.001, HER2 q < 0.0001, CCNE1 q < 0.0001, CCND1 q < 0.001, CDK6 q = 0.0003, BRAF q = 0.0002, MET q = 0.01). FS, frameshift; IF, in-frame.
