Fig. 1
Liquid biopsy identifies actionable dynamic predictors of T-DM1 resistance. a, b HER2 amplification levels were assessed by dPCR in a archival tissues (primary vs metastatic lesions, from left to right), and b serial blood drawings (baseline vs progression). Threshold amplification values in tissues (blue line) and blood (red) are shown. c Box plot showing patient PFS according to the baseline blood HER2 status. Median PFS and standard deviation are indicated in each box plot. d Type, abundance and trends (T0 vs Tp) of circulating alterations. e Blood alterations were ranked by trend, consistency and magnitude (slope of the change, straight and slanted arrows). Alterations consistently increasing and decreasing in all patients were color-coded red and green, respectively, whereas inconsistent trends were shown in blue. f Violin plot showing PFS of patients with ‘red’ and ‘green’ alterations, respectively. Arrows highlight ‘green’ outliers, e.g. two patients progressing due to brain metastasis with no evidence of increase in blood alterations. The dotted vertical line represents median PFS. g Target alterations detected during T-DM1 administration (left panels) were monitored at the time of progression and during subsequent off-label treatments, as indicated. Red, blue and green dots identify WT, mutated and double dPCR positives. Copies/ml of WT (red + green) and mutated (blue + green) DNAs in blood plasma are indicated. *: patient still on T-DM1 treatment. PFS: progression-free survival. VAF: variant allele frequency. Cap: Capecitabine. Exe: Exemestane. Eve: Everolimus. F: Fulvestrant