Extended Data Fig. 3: Genomic features are conserved though elevated through metastasis.

a) Pareto front projection with tumours colored by presence of co-amplification of two or more amplifications in the following cytobands: 17q23 (IC1), 11q13 (IC2), 17q12 (IC5/HER2 + ), 8p12 (IC6) or 8q24 (IC9). b) Pareto front projection with tumours colored by HRD and ER status. c) Barplot shows the proportion and number of samples predicted to be BRCA1-like or BRCA2-like across the subgroups. d) Proportion of various SV events in BRCA1-like, BRCA2-like or non-HRD tumours across the subgroups. e) Replication of the Pareto front projection using the GEL (primary) cohort. Each dot represents the architecture profile of each tumour colored by IC subgroup. f) Activity of six SV signatures across the IC subgroups in metastatic tumours. g) Distribution of primary and metastatic tumours on Pareto front. h) Comparison of SV signatures in primary and metastatic tumours across the IC subgroups. Barplot shows the log fold change of each rearrangement signature between primary and metastatic tumors across the IC subgroups. i) Transition vector corresponding to the difference in position on the Pareto fronts from (g) between the centroid of primary samples and the centroid of metastatic samples in each IC group. j) Replication of the Pareto front projection using the METABRIC (primary) cohort. Each dot represents the architecture profile of each tumour colored by IC subgroup. k) Forest plot shows the association between the proportion of archetypes and distant relapse free (DRF) survival, correcting for ER and HER2. Dots correspond to estimated hazard ratios and segments to 95% confidence intervals. l) Association between recurrence in the ER+ Typical-risk samples and the distance to each archetype (spanning from 0 to 1, linear regression, top), transcriptomic proliferative and HRD LOH scores (linear regression, bottom) and histological type (IDC or ILC, fisher’s exact test, bottom) in the METABRIC dataset. Significance: P ≤ 0.05 (*), P ≤ 0.01 (**), and P ≤ 0.001 (***). m) Differential pattern of relapse across ER + IC subgroups and by histology (IDC: invasive ductal carcinoma and ILC: invasive lobular carcinoma), illustrated by the cumulative (black) and annual (red) risk of relapse. n) ER+ Typical IDC and ILC distribution on the Primary-Discovery Pareto front. o) ER+ Typical IDC and ILC distribution on the METABRIC Pareto front. SV, structural variant; WGD, whole-genome doubling; HRD, homologous repair deficiency; LOH, loss-of-heterozygosity; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma.