Introduction: Homologous recombination deficiency (HRD) is a key biomarker in the management of high-grade serous ovarian cancer (HGSOC), guiding treatment decisions, particularly regarding the use of poly(ADP-ribose) polymerase inhibitors (PARPi). As multiple HRD assays are available, each with distinct methodologies and cutoff values, the interpretation and clinical application of HRD testing remain complex. This intergroup statement, endorsed by the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss, aims to provide guidance on the indications, appropriate use, and limitations of HRD testing in ovarian cancer.
Materials And Methods: The statement is based on an interdisciplinary review of available literature, clinical trial data, and expert consensus. The recommendations focus on the current landscape of HRD assays, their clinical applicability, and practical considerations regarding the optimal timing and indications for testing.
Results And Discussion: Various HRD assays, including established commercial tests and emerging academic-clinical approaches, are reviewed in this statement. The document outlines key eligibility criteria for HRD testing in ovarian cancer, emphasizing its relevance in specific histological subtypes and clinical scenarios. Additionally, exclusion criteria are defined, highlighting cases where HRD testing may not be appropriate due to insufficient clinical validation or lack of therapeutic implications. Finally, the statement discusses the pathological minimum requirements for tissue samples used in HRD testing, ensuring adequate sample quality and tumor content for reliable results.
Conclusion: HRD testing is a valuable tool for personalizing ovarian cancer treatment, particularly in identifying patients who may benefit from PARPi therapy. However, assay selection, timing, and result interpretation require careful consideration. This statement provides a structured approach to optimize HRD testing, aiming to improve clinical decision-making and patient outcomes.
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http://dx.doi.org/10.1007/s00404-025-07991-y | DOI Listing |
Arch Gynecol Obstet
March 2025
Department for Gynecology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Introduction: Homologous recombination deficiency (HRD) is a key biomarker in the management of high-grade serous ovarian cancer (HGSOC), guiding treatment decisions, particularly regarding the use of poly(ADP-ribose) polymerase inhibitors (PARPi). As multiple HRD assays are available, each with distinct methodologies and cutoff values, the interpretation and clinical application of HRD testing remain complex. This intergroup statement, endorsed by the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss, aims to provide guidance on the indications, appropriate use, and limitations of HRD testing in ovarian cancer.
View Article and Find Full Text PDFGenomics Proteomics Bioinformatics
February 2025
Department of In Vitro Diagnostic Reagent, National Institutes for Food and Drug Control (NIFDC), Beijing 100050, China.
Homologous recombination deficiency (HRD) has emerged as a critical prognostic and predictive biomarker in oncology. However, current testing methods, especially those reliant on targeted panels, are plagued by inconsistent results from the same samples. This highlights the urgent need for standardized benchmarks to evaluate HRD assay performance.
View Article and Find Full Text PDFFront Mol Biosci
February 2025
Oncoclínicas&Co, São Paulo, Brazil.
Background: Along with mutation status, homologous recombination deficiency (HRD) testing is a prognostic and predictive biomarker for poly-ADP-ribose polymerase (PARP) inhibitor therapy indication in high-grade epithelial ovarian, fallopian tube, or peritoneal cancer. Approximately 50% of high-grade serous ovarian cancers exhibit HRD, even in the absence of germline or somatic 1/2 loss-of-function mutations. In this scenario, access to a validated diagnostic HRD test can optimize treatment selection and increase the effectiveness of the intervention.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
February 2025
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland.
Background: Although the combined treatment with radiopharmaceutical therapy (RPT) and poly (ADP-ribose) polymerase inhibitors (PARPi) shows promise, a critical challenge remains in the limited quantitative understanding needed to optimize treatment protocols. This study introduces a mathematical model that quantitatively represents homologous recombination deficiency (HRD) and facilitates patient-specific customization of therapeutic schedules.
Methods: The model predicts therapeutic outcomes based on the absorbed dose by DNA and the resulting radiobiological responses, with DNA double-strand breaks (DSBs) being the critical determinant of cancer cell fate.
Curr Oncol
February 2025
Institute for Clinical Genetics and Genomics, Showa University, Tokyo 142-8555, Japan.
Recently, homologous recombination deficiency (HRD) has become a new target for hereditary cancers. Molecular-based approaches for hereditary cancers in the clinical setting have been reviewed. In particular, the efficacy of the inhibitor has been considered by several clinical trials for various kinds of hereditary cancers.
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