Jonathan T. Lei1, Eric J. Jaehnig1, Hannah Smith2, Matthew V. Holt1, Xi Li2, Meenakshi Anurag1, Matthew J. Ellis1,3, Gordon B. Mills2, Bing Zhang1 and Marilyne Labrie2,4,5 1Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA 2Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, USA Correspondence: millsgohsu.edu; bing.zhangbcm.edu; marilyne.labrieusherbrooke.ca

↵3 Present address: Early Oncology, Oncology Research and Development, AstraZeneca, Gaithersburg, MD 20878.

↵4 Present address: Department of Immunology and Cellular Biology, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

↵5 Present address: Department of Obstetrics and Gynecology, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

The goal of precision oncology is to translate the molecular features of cancer into predictive and prognostic tests that can be used to individualize treatment leading to improved outcomes and decreased toxicity. Success for this strategy in breast cancer is exemplified by efficacy of trastuzumab in tumors overexpressing ERBB2 and endocrine therapy for tumors that are estrogen receptor positive. However, other effective treatments, including chemotherapy, immune checkpoint inhibitors, and CDK4/6 inhibitors are not associated with strong predictive biomarkers. Proteomics promises another tier of information that, when added to genomic and transcriptomic features (proteogenomics), may create new opportunities to improve both treatment precision and therapeutic hypotheses. Here, we review both mass spectrometry-based and antibody-dependent proteomics as complementary approaches. We highlight how these methods have contributed toward a more complete understanding of breast cancer and describe the potential to guide diagnosis and treatment more accurately.