Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes

Despite the advancement of genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein level information. Formalin-fixed paraffin-embedded (FFPE) tissue specimens are widely available and can be directly linked to extended clinical outcomes. We performed comprehensive proteomic profiling of 300 FFPE breast cancer surgical specimens, 75 of each PAM50 subtype, with linked clinical outcomes. Using our highly sensitive SP3-Clinical Tissue Proteomics platform, we quantified 4214 proteins across all 300 samples. The analysis identified a distinct proteomic group characterized by high expression of immune response proteins and favorable survival rates. Four clinically distinct proteomic clusters within samples classified as triple negative breast cancer by immunohistochemistry had features of “basal-immune hot”, “basal-immune cold”, “mesenchymal”, and “luminal androgen receptor”. Our proteomic analysis characterizes the heterogeneity of breast cancer in a clinically-applicable manner, identifies potential biomarkers and therapeutic targets, and provides a resource for clinical breast cancer classification.