Triple Negative Breast Cancer (TNBC) is recognised as heterogeneous, with distinct subtypes specified by histopathologic and gene expression analysis. However, these do not align closely to treatment response and there is an on-going need for both clinically applicable biomarkers and new effective treatments. Comprehensive profiling of the TNBC tissue proteome has potential to bring new perspective to these challenges. We report global proteomic profiles of 312 TNBC cases derived from Data Independent Acquisition-Mass Spectrometry (DIA-MS) analysis, coupled with gene expression profiling in a subset of cases (n = 97). This showed differential expression of protein cassettes reflecting the key features of 1) cellular growth and proliferation, 2) immune activation, 3) mesenchymal elements and 4) luminal androgen receptor phenotype. In combination, these cassettes distinguished TNBC subtypes that align to potential treatments. We also found an association between immune activation and improved survival that was influenced by the presence of lymph node metastases. In our cohort and in a validation dataset, the combination of a five protein immune activation signature with lymph node status was highly predictive of survival, suggesting that a combination of tissue proteomics with clinical features could be an informative guide to TNBC management. This large proteomic study forms a resource to progress this goal.
Doan et al. (Thu,) studied this question.