Fig. 3: Clinical and pathological associations of breast cancer mutation profile.

a Association of number of mutations (SNVs/indels, left) and the maximum variant allele frequency (mVAF, right, as a proxy of ctDNA purity) with indicated clinical and pathological features. p values from pairwise two-sided Kruskal–Wallis test with correction for multiple testing (number of mutations: HR + HER2- vs TNBC q = 0.008; 0 vs ≥5 lines of treatment q = 0.0005, 1–2 vs ≥5 lines of treatment q = 0.0005; 0 vs ≥3 lines of chemotherapy q = 0.003. mVAF: 0 vs ≥5 lines of treatment q = 0.03, 1–2 vs ≥5 lines of treatment q = 0.006; 0 vs 1–2 lines of chemotherapy q = 0.003, 0 vs ≥3 lines of chemotherapy q = 0.0003; soft tissue/nodal vs visceral disease q = 0.002). MBC, metastatic breast cancer; CTx, chemotherapy; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. b Association of clinical and pathological features with pathogenic alterations in the four targetable genes in plasmaMATCH: PIK3CA, ESR1, HER2 and AKT1. p-values from Chi-squared test (PIK3CA: histological subtype p < 0.0001, lines of treatment p = 0.006; ESR1: histological subtype p < 0.0001, lines of treatment p < 0.0001, disease site p = 0.003; HER2: histological subtype p = 0.004, primary breast cancer subtype p < 0.0001). c HER2 mutation incidence in patients with HER2 + cancer, by line of therapy. 0–1 lines of therapy mutation incidence 7.3% (3/41) and 2–3 lines of therapy mutation incidence 25% (8/32) HER2 mutations, p = 0.04, Chi-squared test. mt, mutant; wt wild-type. d) Adjusted HER2 copy number (CN) in targeted sequencing, in patients with tissue assessed HER2 + (amplified, N = 72) and HER2- (non-amplified, N = 605) cancers. (left) receiver operator curve of adjusted HER2 plasma copy number, (right) HER2 plasma copy number adjusted for purity. Data are presented as mean + SD. The p-value indicated is derived from a two-sided Mann–Whitney U-test.