(A) Chromosome zoom-in-views of regions affected by copy number heterogeneity that are important in breast cancer genomes. Categories are: regions recurrently altered by CNA, regions harboring therapeutically relevant genes, regions harboring genes known to be recurrently altered by SNV, and regions harboring genes for which experimental evidence exists for importance in the metastatic process. (B) DNA-FISH validation of a selected subset of heterogeneous CNAs. The selected alterations are: Chromosome 16q and 16 p sub-clonality seen in HER2+ tumor P14 (left panel) and PIK3CA sub-clonality in a LumA tumor, P5 (right panel). (C) Distant relapse-free survival curves for all METABRIC cases with 1q/8q gains(n = 446). Within the cohort that was ER+/HER2-, survival curves are also shown for patients that are lymph node positive (LN+, n = 192) and lymph node negative (LN-, n = 236). (D) Contingency table summarizing the relationship between high- vs. low-level 1q/8q amplification and IntClust (IC) subtype1 for all METABRIC cases with 1q/8q amplification. Among high risk ER+/HER2- groups (IC 1,2,6,9)2, IC9 has the highest rate of high level 1q/8q amplifications. A t-test for proportions between IC 9 (high risk) vs IC 3 (lower risk) shows that high-level 1q/8q amplifications are statistically significantly more likely to occur in IC9 (p-value=3.021e-07).