Blood-Based mRNA Tests as Emerging Diagnostic Tools for Personalised Medicine in Breast Cancer

SIMPLE SUMMARY: Molecular diagnostic tests can facilitate molecular classification of breast cancer and its clinical management, including prediction, prognosis, and selection of therapy. Messenger RNA tests can supplement the clinically widely used DNA genetic testing. For instance, they can offer valuable information beyond DNA in cases where DNA variants are difficult to interpret. Moreover, several tissue-based mRNA tests for breast cancer are already used routinely in clinical practice to assess the recurrence risk and guide adjuvant endocrine therapy and chemotherapy. Here, we bring attention to the recently developed and commercially available blood mRNA diagnostic tests for breast cancer, which offer several advantages over tissue-based tests, including minimal invasiveness, absence of heterogeneity problems, cost-efficiency, and possibilities for early cancer detection well before the currently used conventional diagnostic approaches. We also investigate the state-of-the-art blood transcriptomic breast cancer research aimed at bringing novel blood transcriptome biomarkers and next-generation sequencing technology into clinical practice. ABSTRACT: Molecular diagnostic tests help clinicians understand the underlying biological mechanisms of their patients’ breast cancer (BC) and facilitate clinical management. Several tissue-based mRNA tests are used routinely in clinical practice, particularly for assessing the BC recurrence risk, which can guide treatment decisions. However, blood-based mRNA assays have only recently started to emerge. This review explores the commercially available blood mRNA diagnostic assays for BC. These tests enable differentiation of BC from non-BC subjects (Syantra DX, BCtect), detection of small tumours <10 mm (early BC detection) (Syantra DX), detection of different cancers (including BC) from a single blood sample (multi-cancer blood test Aristotle), detection of BC in premenopausal and postmenopausal women and those with high breast density (Syantra DX), and improvement of diagnostic outcomes of DNA testing (variant interpretation) (+RNAinsight). The review also evaluates ongoing transcriptomic research on exciting possibilities for future assays, including blood transcriptome analyses aimed at differentiating lymph node positive and negative BC, distinguishing BC and benign breast disease, detecting ductal carcinoma in situ, and improving early detection further (expression changes can be detected in blood up to eight years before diagnosing BC using conventional approaches, while future metastatic and non-metastatic BC can be distinguished two years before BC diagnosis).