Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

SIMPLE SUMMARY: Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous breast cancer (BC) type which is difficult to treat and accompanied by disease recurrence. A better understanding of TNBC and the identification of novel biomarkers is needed to facilitate clinical decisions. Immune-related biomarkers are of particular interest, since immune responses play an important role in BC outcome. Transcriptome studies of peripheral blood cells can help us to understand the systemic immune responses to cancer cells and the mechanisms underlying cancer initiation and progression. They enable the identification of novel immune biomarkers for early cancer detection and personalized BC management and may bring forward new immunotherapy options. Recent transcriptome analyses of peripheral blood cells have delineated novel BC-patient immune subgroups. This categorization has implications for cancer prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Additionally, transcriptome studies have identified TNBC-enriched blood transcriptional signatures that can differentiate TNBC from other classical BC subtypes. ABSTRACT: Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.