Homologous Recombination Deficiency Detection Algorithms: A Systematic Review

Simple Summary Homologous recombination deficiency (HRD) originates from genomic mutations or alterations in the homologous recombination repair pathway. Various promising tests have been developed to detect HRD. Some of these tests have shown good ability to predict response to Poly (ADP-ribose) polymerase inhibitors in cancer patients. However, a standardized way to define HRD has yet to be established. In this systematic review an overview of available HRD tests is provided. Important factors to consider are highlighted when planning clinical trials and studies involving HRD tests.Abstract Homologous recombination deficiency (HRD) can arise from germline or somatic pathogenic variants as well as other genomic damage and epigenetic alterations in the HR repair pathway. Patients with tumors presenting with an HRD phenotype can show sensitivity to Poly (ADP-ribose) polymerase inhibitors (PARPis). Several promising tests to detect HRD have been developed based on different HRD definitions, biomarkers, and algorithms. However, no consensus on a gold standard HRD test has been established. In this systematic review, a comprehensive list of tests for the detection of HRD was identified and compared regarding HRD definition, biomarkers, and algorithms. PubMed's Medline and Elsevier's Embase were systematically searched, resulting in 27 eligible articles meeting the inclusion criteria. The primary challenge when comparing HRD tests lies in the lack of a consensus definition of HRD, as the HRD definition influences the proportion of samples being classified as HRD and impacts the classification performance. This systematic review provides an overview of available HRD tests that can inspire other researchers in searching for a gold standard HRD definition and highlights the importance of the factors that should be considered when choosing an HRD definition and tests for future planning of clinical trials and studies.