The study presents an integrated analysis of copy number and gene expression in a large cohort of primary breast tumors, aiming to identify novel subgroups and their molecular drivers. The analysis includes 997 primary tumors for discovery and 995 for validation, with long-term clinical follow-up. Key findings include: 1. **Genomic and Transcriptomic Impact**: Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in about 40% of genes, with CNAs dominating the landscape in both cis and trans acting effects. 2. **Expression Outliers and Putative Cancer Genes**: By identifying expression outliers driven by *cis* CNAs, the study identified putative cancer genes such as *PPP2R2A*, *MTAP*, and *MAP2K4*, which were deleted in breast cancers. 3. **Novel Subgroups with Distinct Clinical Outcomes**: Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, including a high-risk, oestrogen-receptor-positive 11q13/14 *cis*-acting subgroup and a favorable prognosis subgroup devoid of CNAs. 4. **Trans-acting aberration hotspots**: These hotspots modulated subgroup-specific gene networks, such as a TCR deletion-mediated adaptive immune response in the 'CNA-devoid' subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. 5. **Molecular Stratification**: The results provide a novel molecular stratification of breast cancer, derived from the impact of somatic CNAs on the transcriptome, and highlight the importance of integrating multiple genomic features for robust patient classification. The study underscores the significance of integrating multiple genomic views to better understand the molecular architecture of breast cancer and to identify potential therapeutic targets.The study presents an integrated analysis of copy number and gene expression in a large cohort of primary breast tumors, aiming to identify novel subgroups and their molecular drivers. The analysis includes 997 primary tumors for discovery and 995 for validation, with long-term clinical follow-up. Key findings include: 1. **Genomic and Transcriptomic Impact**: Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in about 40% of genes, with CNAs dominating the landscape in both cis and trans acting effects. 2. **Expression Outliers and Putative Cancer Genes**: By identifying expression outliers driven by *cis* CNAs, the study identified putative cancer genes such as *PPP2R2A*, *MTAP*, and *MAP2K4*, which were deleted in breast cancers. 3. **Novel Subgroups with Distinct Clinical Outcomes**: Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, including a high-risk, oestrogen-receptor-positive 11q13/14 *cis*-acting subgroup and a favorable prognosis subgroup devoid of CNAs. 4. **Trans-acting aberration hotspots**: These hotspots modulated subgroup-specific gene networks, such as a TCR deletion-mediated adaptive immune response in the 'CNA-devoid' subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. 5. **Molecular Stratification**: The results provide a novel molecular stratification of breast cancer, derived from the impact of somatic CNAs on the transcriptome, and highlight the importance of integrating multiple genomic features for robust patient classification. The study underscores the significance of integrating multiple genomic views to better understand the molecular architecture of breast cancer and to identify potential therapeutic targets.