Volatile Organic Compounds Analysis as a Potential Novel Screening Tool for Breast Cancer: A Systematic Review

Introduction: An early diagnosis is crucial in reducing mortality among people who have breast cancer (BC). There is a shortfall of characteristic early clinical symptoms in BC patients, highlighting the importance of investigating new methods for its early detection. A promising novel approach is the analysis of volatile organic compounds (VOCs) produced and emitted through the metabolism of cancer cells. Methods: The purpose of this systematic review is to outline the published research regarding BC-associated VOCs. For this, headspace analysis of VOCs was explored in patient-derived body fluids, animal model-derived fluids, and BC cell lines to identify BC-specific VOCs. A systematic search in PubMed and Web of Science databases was conducted according to the PRISMA guidelines. Results: Thirty-two studies met the criteria for inclusion in this review. Results highlight that VOC analysis can be promising as a potential novel screening tool. However, results of in vivo , in vitro and case-control studies have delivered inconsistent results leading to a lack of inter-matrix consensus between different VOC sampling methods. Discussion: Discrepant VOC results among BC studies have been obtained, highly due to methodological discrepancies. Therefore, methodological issues leading to disparities have been reviewed and recommendations have been made on the standardisation of VOC collection and analysis methods for BC screening, thereby improving future VOC clinical validation studies.