Shotgun proteomics of archival triple-negative breast cancer samples

Purpose: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers, and has a worse prognosis compared with hormone receptor-positive disease. Its unfavorable outcome and the lack of hormonal receptors determine the use of adjuvant chemotherapy as part of the standard treatment for these tumors, although several studies have documented that the current standard combination chemotherapy is suboptimal. Therefore, a new functional taxonomy of breast cancer and new targets for therapeutic development are urgently needed. Experimental design: In this study, we have analyzed the proteome of TNBC applying a high-throughput proteomics approach to routinely archived formalin-fixed, paraffin-embedded tumor tissues. Results: We have been able to identify and quantify more than 1000 protein groups. Some of these proteins are of outstanding interest in the biology and clinical management of this disease, such as CD44 and PARP1. Moreover, we have characterized some signaling pathways that could be related to TNBC genesis and development. Conclusion and clinical relevance: Our results open up new avenues for the use of proteomics technologies in clinically relevant studies using archival samples. Shotgun LC-MS/MS studies could serve to discover new biomarkers and may provide clues to the genesis of TNBC and underlying molecular alterations.