Updated project metadata. Molecular profiling of breast cancer has achieved great depth in defining the mutational landscapes and molecular profiles of primary tumors, though little is still known regarding cancer evolution into a recurrence. Proteogenomic workflows are particularly useful in defining the multi-layered biology of complex diseases by combining genomic, transcriptomic, and proteomic technologies so to inform not only on mutational processes, but also on their repercussion at the effector level, proteins. We employed our recently developed proteogenomic workflow to analyze a cohort of 27 primary breast cancers and their matched loco-regional recurrences by whole genome sequencing, RNA sequencing, and mass spectrometry.