{"product_id":"hrd-testing-in-advanced-ovarian-cancer-a-patient-guide-to-the-2025-intergroup-statement","title":"HRD Testing in Advanced Ovarian Cancer: A Patient Guide to the 2025 Intergroup Statement","description":"\u003cp\u003eA new intergroup position statement from the German Ovarian Cancer Commission, NOGGO, AGO Austria, and AGO Swiss explains how doctors should use homologous recombination deficiency (HRD) testing in advanced ovarian cancer. HRD is a biomarker — a measurable biological signal — that helps identify which patients are likely to benefit from PARP inhibitors (PARPi), a class of oral maintenance drugs. The statement reviews every major HRD assay category, defines who should and should not be tested, and sets minimum quality standards for tumor tissue samples. The authors stress that test choice, timing, and interpretation near cutoff values all require careful interdisciplinary discussion.\u003c\/p\u003e\n\n\u003ch1\u003eHRD Testing in Advanced Ovarian Cancer: A Patient Guide to the 2025 Intergroup Statement\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eWhy This Statement Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow This Statement Was Developed\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#hrd-definition\"\u003eWhat Is HRD? Understanding DNA Repair and Ovarian Cancer\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#parpi\"\u003eHow PARP Inhibitors Exploit HRD\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#landscape\"\u003eThe Landscape of HRD Tests\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#approved-tests\"\u003eClinically Approved Tests Available in Germany\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#emerging-tests\"\u003eEmerging Tests and Bridging Concordance\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#cutoffs\"\u003eCutoff Values: A Critical Practical Issue\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#statement\"\u003eThe Official Recommendations of the Intergroup\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#when-to-test\"\u003eWhen HRD Testing Is Appropriate\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#when-not-to-test\"\u003eWhen HRD Testing Is Not Recommended\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#pathology\"\u003eMinimum Standards for Tumor Tissue Samples\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations and Open Questions\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Advice for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eHRD testing helps identify patients with advanced ovarian cancer likely to benefit from PARP inhibitors, but it is not a single uniform test.\u003c\/li\u003e\n\u003cli\u003eA positive germline BRCA1\/2 result makes further HRD testing unnecessary; a negative result allows HRD testing as a second step.\u003c\/li\u003e\n\u003cli\u003eHRD testing is relevant for high-grade serous, endometrioid, clear cell carcinoma, and carcinosarcoma, but not low-grade epithelial ovarian carcinoma.\u003c\/li\u003e\n\u003cli\u003eReliable results need tissue at least 5 mm in diameter with at least 30% tumor cells; lymph node samples may have much lower tumor content.\u003c\/li\u003e\n\u003cli\u003eResults near a test cutoff are uncertain and should be discussed by an interdisciplinary team before a final treatment decision.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eWhy This Statement Matters\u003c\/h2\u003e\n\u003cp\u003eOvarian cancer treatment has changed dramatically in the past decade. The reason is a class of drugs called PARP inhibitors (PARPi), which work best in tumors that carry a specific weakness in their DNA repair machinery.\u003c\/p\u003e\n\u003cp\u003eThat weakness is called homologous recombination deficiency, or HRD. Testing for HRD helps doctors decide who should receive maintenance therapy after initial treatment. But there is a problem: many different HRD tests exist, and they do not all measure the same thing or use the same cutoffs.\u003c\/p\u003e\n\u003cp\u003eThis intergroup statement was written to bring clarity. It is endorsed by four organizations: the German Ovarian Cancer Commission, the North-Eastern German Society of Gynecological Oncology (NOGGO), AGO Austria, and AGO Swiss. Its goal is simple — help clinicians decide when to order HRD testing, which test to choose, and how to interpret the result.\u003c\/p\u003e\n\u003cp\u003eFor patients, the practical takeaway is this: HRD testing is not a single, uniform test. Where and when it is done, and which laboratory performs it, can affect your treatment options.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow This Statement Was Developed\u003c\/h2\u003e\n\u003cp\u003eThe statement is not a clinical trial. It is a consensus document, meaning it reflects expert agreement rather than new experimental data.\u003c\/p\u003e\n\u003cp\u003eThe authors performed an interdisciplinary review of three sources of information: the available published literature, data from major clinical trials, and expert consensus among the participating groups. The resulting recommendations focus on three areas. First, the current landscape of HRD assays, including their different methodologies. Second, the clinical applicability of these tests — meaning where they actually change treatment decisions. Third, practical considerations about the best timing and the right indications for testing.\u003c\/p\u003e\n\u003cp\u003eThe document also defines exclusion criteria. These are situations where HRD testing is not appropriate, either because the test has not been sufficiently validated or because the result would not change what doctors would do. Finally, it sets out the minimum pathological requirements for tissue samples, so that results are reliable.\u003c\/p\u003e\n\n\u003ch2 id=\"hrd-definition\"\u003eWhat Is HRD? Understanding DNA Repair and Ovarian Cancer\u003c\/h2\u003e\n\u003cp\u003eGenomic instability (GIS) — a state in which the genome accumulates errors — is one of the most common causes of tumorigenesis (the formation of cancer). Cells have several DNA repair systems that normally keep the genome stable. One of the most important is the homologous recombination repair (HRR) system.\u003c\/p\u003e\n\u003cp\u003eDuring genomic replication (the process of copying DNA), two dangerous types of damage can occur: double-strand breaks and interstrand cross-links (ICL, abnormal chemical bonds that link the two DNA strands together). The HRR system responds to these problems using its specialized proteins to repair the damage.\u003c\/p\u003e\n\u003cp\u003eWhen the HRR pathway is defective — because of genetic (inherited or acquired) or epigenetic changes — the result is the phenotype (observable characteristic) known as homologous repair deficiency, or HRD. In plain terms, the cell loses its ability to repair double-strand breaks.\u003c\/p\u003e\n\u003cp\u003eOnce HRD is present, genomic instability can develop and spread. GIS shows up in three measurable patterns used by HRD tests:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGenomic loss of heterozygosity (gLOH)\u003c\/strong\u003e — the loss of one of the two copies of a gene region in the tumor.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTelomeric imbalance (TAI)\u003c\/strong\u003e — an imbalance in the lengths of telomeres, the protective caps at the ends of chromosomes, between the two alleles of a gene.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLarge-scale transitions (LST)\u003c\/strong\u003e — structural changes in chromosomes on a large scale, such as rearrangements, copy number alterations, or changes in chromosome arm status.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eIn high-grade serous ovarian cancer (HGSOC) specifically, the HRR system plays a major role in how the cancer develops. Germline and somatic mutations in the breast-cancer genes BRCA1 and BRCA2 are the main cause of HRR pathway defects.\u003c\/p\u003e\n\u003cp\u003eThe numbers matter here. Approximately \u003cstrong\u003e13 to 15% of patients with HGSOC\u003c\/strong\u003e carry a germline (inherited) mutation in BRCA1 or BRCA2. Up to \u003cstrong\u003e3 to 7%\u003c\/strong\u003e have somatic mutations — mutations that arise in the tumor itself, not inherited from parents.\u003c\/p\u003e\n\u003cp\u003eBut BRCA1 and BRCA2 are not the only genes involved. Many other genes can lead to HRD, including BARD1 (BRCA1-associated RING domain 1), BRIP1 (BRCA-interacting protein 1), CHEK1 (checkpoint kinase 1), CHEK2 (checkpoint kinase 2), FAM175A, NBN (nibrin), PALB2 (partner and localizer of BRCA2), RAD51C, RAD51D, \"and many more,\" as the authors note.\u003c\/p\u003e\n\n\u003ch2 id=\"parpi\"\u003eHow PARP Inhibitors Exploit HRD\u003c\/h2\u003e\n\u003cp\u003eThe clinical importance of HRR defects became clear with the arrival of poly(ADP-ribose) polymerase inhibitors (PARPi). These drugs block base excision repair — a different DNA repair pathway that fixes single-strand breaks.\u003c\/p\u003e\n\u003cp\u003eWhen base excision repair is blocked, single-strand breaks accumulate during DNA replication. This causes the repair system to collapse and creates double-strand breaks. In cells with HRD, those breaks cannot be repaired properly. The result is a process called synthetic lethality — the cancer cell dies because it has lost two repair mechanisms at once.\u003c\/p\u003e\n\u003cp\u003eSeveral major trials demonstrated that PARPi work as maintenance therapy (treatment given after the main therapy to keep the cancer from returning) in HGSOC. The statement cites:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSOLO1\u003c\/strong\u003e — olaparib monotherapy (given alone).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePAOLA1\u003c\/strong\u003e — the combination of olaparib plus bevacizumab.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePRIMA\u003c\/strong\u003e — niraparib monotherapy.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThese trials led to approval by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA).\u003c\/p\u003e\n\u003cp\u003eBRCA germline mutations were the first marker understood as predicting effective PARPi use. Then the PAOLA1 trial showed something broader. Patients with pathogenic BRCA1\/2 mutations benefited from olaparib maintenance — \u003cem\u003eand so did patients whose tumors showed genomic instability on the Myriad MyChoice assay\u003c\/em\u003e, even without a BRCA mutation.\u003c\/p\u003e\n\u003cp\u003eThis finding elevated the importance of other HRD-related genes. The authors argue that including these genes in routine testing for ovarian cancer patients is warranted, because it allows clinicians to make well-grounded decisions about PARPi use.\u003c\/p\u003e\n\n\u003ch2 id=\"landscape\"\u003eThe Landscape of HRD Tests\u003c\/h2\u003e\n\u003cp\u003eDifferent tests are available to determine HRD status. The statement organizes them into three broad categories.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e1. Next-generation sequencing (NGS) assays.\u003c\/strong\u003e These analyze genomic DNA to detect mutations in genes associated with HRD, such as BRCA1 and BRCA2, plus other HRD-related genes. Within this category:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGenetic testing:\u003c\/strong\u003e BRCA1 and BRCA2 mutations are well-established indicators of HRD, particularly in breast and ovarian cancers. Genetic testing can identify these mutations, and their presence suggests HRD. Testing methods include targeted sequencing, multiplex ligation dependent probe amplification (MLPA), and next-generation sequencing (NGS).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHomologous Recombination Deficiency Score (HRD Score):\u003c\/strong\u003e some commercial tests, such as the Myriad myChoice® HRD test, calculate a score based on multiple genomic markers associated with HRD. This score predicts HRD and guides treatment decisions. It includes measures of genomic instability such as loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LSTs).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e2. Genomic instability assays.\u003c\/strong\u003e These measure genomic instability directly through three features:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLoss of Heterozygosity (LOH) testing:\u003c\/strong\u003e LOH is a common feature of HRD, marked by the loss of one of the two copies of a gene in a tumor. LOH testing identifies regions of the genome where one copy has been lost, indicating HRD.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTelomeric allelic imbalance (TAI):\u003c\/strong\u003e an imbalance in telomere lengths between the two alleles of a gene. TAI is a form of genomic instability that can indicate defects in DNA repair pathways such as HRR, and it is associated with certain cancers, including ovarian cancer.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLarge-scale state transitions (LSTs):\u003c\/strong\u003e structural genomic alterations occurring on a large scale, involving changes in chromosomal structure or organization. These may include chromosomal rearrangements, copy number alterations, or changes in chromosome arm status.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e3. Functional assays.\u003c\/strong\u003e These evaluate how well the HRD repair pathways actually work in cells. They typically use laboratory-based experiments measuring the ability of cells to repair DNA damage — for example, the RAD51 Foci assay.\u003c\/p\u003e\n\n\u003ch2 id=\"approved-tests\"\u003eClinically Approved Tests Available in Germany\u003c\/h2\u003e\n\u003cp\u003eThe statement lists the following tests as clinically approved and commonly accessible in Germany. This table preserves the original details on mechanism, what counts as HRD-positive, the patient sample required, and the trial in which each was evaluated.\u003c\/p\u003e\n\n\u003ctable\u003e\n  \u003cthead\u003e\n    \u003ctr\u003e\n      \u003cth\u003eTest name\u003c\/th\u003e\n      \u003cth\u003eMechanism\u003c\/th\u003e\n      \u003cth\u003eHRD-positive\u003c\/th\u003e\n      \u003cth\u003ePatient's probe\u003c\/th\u003e\n      \u003cth\u003eTrial evaluated\u003c\/th\u003e\n    \u003c\/tr\u003e\n  \u003c\/thead\u003e\n  \u003ctbody\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eBRACAnalysis CDx test (genetic testing)\u003c\/td\u003e\n      \u003ctd\u003eGermline mutation in BRCA1\/2\u003c\/td\u003e\n      \u003ctd\u003eMutation detectable\u003c\/td\u003e\n      \u003ctd\u003eBlood\u003c\/td\u003e\n      \u003ctd\u003e—\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eMyriad myChoice CDx test\u003c\/td\u003e\n      \u003ctd\u003eMutation status of BRCA1\/2 AND GIS (gLOH + TAI + LST)\u003c\/td\u003e\n      \u003ctd\u003eBRCA mutation OR GIS \u0026gt; 42\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePRIMA \/ PAOLA-1 \/ VELIA \/ NOVA\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eFoundationOne CDx panel\u003c\/td\u003e\n      \u003ctd\u003eMutation status of BRCA1\/2 AND genomic instability (gLOH)\u003c\/td\u003e\n      \u003ctd\u003eBRCA mutation OR LOH-Score ≥ 16%\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003eATHENA Mono \/ ARIEL 2\/3 \/ QUADRA\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eNOGGO GIS assay\u003c\/td\u003e\n      \u003ctd\u003eNGS hybrid-capture biomarker assay detecting BRCA1\/2 plus 55 further HRR-relevant genes and structural alterations to establish GIS\u003c\/td\u003e\n      \u003ctd\u003eBRCA mutation or GIS \u0026gt; 83\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1 cohort\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eGeneva test\u003c\/td\u003e\n      \u003ctd\u003eOncoScan plus number of large-scale state transitions (nLST)\u003c\/td\u003e\n      \u003ctd\u003enLST threshold of 15\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1 cohort\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eAcademic Leuven HRD test\u003c\/td\u003e\n      \u003ctd\u003eTargeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53\u003c\/td\u003e\n      \u003ctd\u003e—\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1 cohort\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eSOPHiA DDM™ Dx HRD Solution\u003c\/td\u003e\n      \u003ctd\u003eDetects SNVs (single nucleotide variants) and Indels in 28 genes involved in the HRR pathway, including BRCA1 and BRCA2\u003c\/td\u003e\n      \u003ctd\u003e—\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1 cohort\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eIllumina TSO 500\u003c\/td\u003e\n      \u003ctd\u003eLow-WGS (shallow whole genome sequencing) for LOH + TAI + LST\u003c\/td\u003e\n      \u003ctd\u003e—\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1 cohort\u003c\/td\u003e\n    \u003c\/tr\u003e\n    \u003ctr\u003e\n      \u003ctd\u003eBRCA-like classifier\u003c\/td\u003e\n      \u003ctd\u003eDiscriminates BRCA-associated from sporadic cancers using the shrunken centroid algorithm; low-WGS\u003c\/td\u003e\n      \u003ctd\u003eBRCA-like \u0026gt; 0.5; non-BRCA-like ≤ 0.5\u003c\/td\u003e\n      \u003ctd\u003eTumor tissue\u003c\/td\u003e\n      \u003ctd\u003ePAOLA-1, AGO-TR1\u003c\/td\u003e\n    \u003c\/tr\u003e\n  \u003c\/tbody\u003e\n\u003c\/table\u003e\n\n\u003ch2 id=\"emerging-tests\"\u003eEmerging Tests and Bridging Concordance\u003c\/h2\u003e\n\u003cp\u003eAdditional tests exist that have not yet been clinically evaluated for progression-free survival (PFS — how long patients live without the cancer getting worse) and overall survival (OS — how long patients live overall). However, these tests show high concordance (agreement) with the Myriad myChoice test. This agreement is referred to as \"bridging.\"\u003c\/p\u003e\n\u003cp\u003eThese emerging tests include:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCytoSNP:\u003c\/strong\u003e a single nucleotide polymorphism (SNP) array for LOH + TAI + LST.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAffymetrix OncoScan:\u003c\/strong\u003e a SNP array for LOH + TAI + LST.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOncoMine:\u003c\/strong\u003e shallow whole genome sequencing (low-WGS) for an LOH score.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAmoyDX:\u003c\/strong\u003e a low-WGS HRD focus panel for detecting BRCA1\/2 mutation and genomic instability — \"and many more,\" the authors add.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eReal-world data have shown that a genomic loss of heterozygosity greater than 16% (gLOH \u0026gt; 16%) and a genomic instability score greater than 42 (GIS \u0026gt; 42) overlap significantly. Clinically, they are comparable with regard to time to treatment discontinuation (TTD) — how long a patient stays on a treatment before it is stopped.\u003c\/p\u003e\n\n\u003ch2 id=\"cutoffs\"\u003eCutoff Values: A Critical Practical Issue\u003c\/h2\u003e\n\u003cp\u003eRegarding the cutoff values of each test, the authors issue an important caution. The 95% confidence intervals (the statistical range within which the true value likely falls) are generally not reported. This means the precision of each cutoff is uncertain.\u003c\/p\u003e\n\u003cp\u003eBecause of this, results near the threshold should be discussed in an interdisciplinary setting — among pathologists, gynecologic oncologists, and other specialists — considering multiple factors and the patient's clinical context. A result just above or just below the cutoff is not always a clear answer.\u003c\/p\u003e\n\n\u003ch2 id=\"statement\"\u003eThe Official Recommendations of the Intergroup\u003c\/h2\u003e\n\u003cp\u003eThe statement includes three formal recommendations.\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003eBecause patients are considered HRD positive — and therefore eligible for maintenance therapy with olaparib — either through a germline or somatic BRCA1\/2 mutation \u003cstrong\u003eOR\u003c\/strong\u003e through a positive genomic instability score, \u003cstrong\u003eboth the GIS and the BRCA1\/2 status must be evaluated together\u003c\/strong\u003e to reach a conclusive result.\u003c\/li\u003e\n  \u003cli\u003eBecause GIS is a continuous marker to which a hard cutoff is applied, ideally all assays used to stratify patients for treatment decisions should have demonstrated effectiveness by providing clinical PFS and ideally OS data. However, in most settings these data are not available, due to limited access to clinical trial specimens.\u003c\/li\u003e\n  \u003cli\u003eA number of assays with their specific cutoffs have been evaluated and validated using tissue samples from the PAOLA-1 clinical trial, made available by the ENGOT\/ARCA GY group. For some of these assays, PFS and OS data are available, and the survival curves show highly comparable results with comparable hazard ratios (a measure of how much a treatment reduces risk). The authors therefore recommend using assays for which a significant clinical benefit — and comparable PFS and OS advantages — has been shown on samples from the PAOLA-1 trial or other clinical trials looking at outcomes in HRD and HRP (homologous recombination proficient) populations.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003ch2 id=\"when-to-test\"\u003eWhen HRD Testing Is Appropriate\u003c\/h2\u003e\n\u003cp\u003eAll patients diagnosed with ovarian cancer should undergo genetic counseling and testing for BRCA1 and BRCA2 and other BRCA-related genes, as recommended by guidelines. This testing is typically included in a broad standardized panel covering the most common mutations associated with hereditary cancer syndromes.\u003c\/p\u003e\n\u003cp\u003eThe statement then sets out criteria that should be considered for further HRD testing:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eContextual relevance:\u003c\/strong\u003e the HRD test must fit within the overall clinical context of the patient's condition and treatment plan. The ability to take oral medications is mandatory, since all PARP inhibitors are taken by mouth.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNegative germline mutations:\u003c\/strong\u003e if germline testing for BRCA1\/2 alone (performed by human genetics) is negative, HRD can be pursued as a second test in a two-step procedure. This can be done immediately after a negative germline result. Ideally, HRD testing should be performed simultaneously with germline testing.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePrimary setting:\u003c\/strong\u003e HRD testing should ideally be conducted after the initial diagnosis, using tumor tissue. If tumor tissue cannot be obtained during cytoreductive surgery (surgery to remove as much tumor as possible), multiple minimally invasive biopsies should be taken to gather sufficient material. The choice of biopsy sites should prioritize obtaining a high tumor sample size to optimize results. Tissue can be collected via laparoscopy (keyhole surgery) or interventional radiology.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHistological subtypes:\u003c\/strong\u003e HRD testing is particularly relevant for certain histological subtypes — that is, the types of cells the tumor is made of. These include high-grade serous, endometrioid, and clear cell epithelial ovarian carcinoma, as well as ovarian carcinosarcoma, following the WHO classification of 2014 (p53-mutated).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"when-not-to-test\"\u003eWhen HRD Testing Is Not Recommended\u003c\/h2\u003e\n\u003cp\u003eThe statement defines several situations where further HRD testing is not eligible or not appropriate.\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePositive germline mutation for BRCA:\u003c\/strong\u003e the use of additional HRD testing is obsolete (unnecessary). The germline result already answers the question.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRecurrent disease or previously treated ovarian cancer:\u003c\/strong\u003e there is a lack of clinical and preclinical trials on this topic. HRD testing may not be reliable in the setting of recurrent disease or pretreated cancer, because alterations in tumor cells and the tumor microenvironment could affect the significance of results. Patients who have already received PARP inhibition or other immunogenic therapy during ovarian cancer treatment should be excluded from testing outside of clinical trials. However, therapies for other, pre-existing cancer sites are not part of this exclusion. If an HRD test was already done in a recurrent disease setting, there is no need to reevaluate HRD again. If no HRD test was done before, and if the result would support the treatment decision-making process, testing can be considered in a recurrence situation on an individual basis.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTumor tissue obtained after neoadjuvant chemotherapy within the primary diagnosis:\u003c\/strong\u003e the significance of an HRD test in tissue obtained after neoadjuvant chemotherapy (chemotherapy given before surgery) at the time of primary diagnosis remains unclear. Tumor necrosis (tumor cell death) at the time of interval surgery can negatively influence the test results.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHistological subtype:\u003c\/strong\u003e all forms of low-grade epithelial ovarian carcinoma, following the WHO classification of 2014, are not eligible for further HRD testing.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"pathology\"\u003eMinimum Standards for Tumor Tissue Samples\u003c\/h2\u003e\n\u003cp\u003eReliable HRD results depend on good-quality tissue. The statement sets minimum requirements for the molecular pathological report, which should include the following information.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e1. Patient identification and short clinical background:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe date of initial diagnosis.\u003c\/li\u003e\n  \u003cli\u003eThe date the test was performed.\u003c\/li\u003e\n  \u003cli\u003eA statement of any previous administration of systemic treatment.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e2. Details on the assay used:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe name of the assay.\u003c\/li\u003e\n  \u003cli\u003eThe assay's performance parameters (specification of the mechanism used within the test).\u003c\/li\u003e\n  \u003cli\u003eThe minimum and maximum tumor cell content.\u003c\/li\u003e\n  \u003cli\u003eA listing of all genes covered by the test.\u003c\/li\u003e\n  \u003cli\u003eConfirmation of sufficiency of sequencing depth (in the case of NGS assays).\u003c\/li\u003e\n  \u003cli\u003eThe cutoff and threshold for a test result.\u003c\/li\u003e\n  \u003cli\u003eA clear statement on the clinical test approval, its eligibility for HRD testing, and the name of the reference.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e3. Details of the specimen taken for testing:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe histological diagnosis (confirmation that high-grade epithelial ovarian cancer is present).\u003c\/li\u003e\n  \u003cli\u003eThe anatomic site where the specimen was taken.\u003c\/li\u003e\n  \u003cli\u003eThe tumor cell content.\u003c\/li\u003e\n  \u003cli\u003eA statement on the adequacy of sample measurements: \u003cstrong\u003ean adequate sample should be at least 5 mm in diameter with at least 30% tumor cell count\u003c\/strong\u003e. CAVE (caution): in lymph node metastasis, the tumor cell count can be low due to a high amount of immunocompetent cells — in such cases it can rapidly fall below 10%.\u003c\/li\u003e\n  \u003cli\u003eCutoff definition: if the HRD score lies a few points beneath the medical approval of a certain drug, a new biopsy to score a higher tumor cell count can be considered. Moreover, off-label use of the drug can be discussed.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e4. BRCA1\/2 status:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eSomatic mutation status of BRCA1\/2, including large deletions and information on LOH of BRCA1\/2.\u003c\/li\u003e\n  \u003cli\u003eClassification of the BRCA mutation according to the consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003e5. Genomic instability score\u003c\/strong\u003e reported as either positive or negative, according to the test-specific cutoff or threshold.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e6. Final HRD status\u003c\/strong\u003e based on BRCA1\/2 mutation status, GIS, and other HRR-relevant genes tested (HRD positive vs. HRD negative).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e7. If applicable,\u003c\/strong\u003e a recommendation of a specific drug and the name of the reference.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\u003cp\u003eThe practical message is that HRD testing is a valuable tool for personalizing ovarian cancer treatment. It helps identify which patients may benefit from PARP inhibitor therapy.\u003c\/p\u003e\n\u003cp\u003eHowever, the statement is equally clear that assay selection, timing, and result interpretation all require careful consideration. Not every test is validated the same way, and not every patient should be tested.\u003c\/p\u003e\n\u003cp\u003eSeveral points deserve emphasis for patients:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eIf your germline BRCA test is positive, you do not need additional HRD testing.\u003c\/li\u003e\n  \u003cli\u003eIf your germline test is negative, HRD testing can still identify whether your tumor has a genomic instability signature that predicts PARPi benefit.\u003c\/li\u003e\n  \u003cli\u003eBoth the BRCA status and the genomic instability score must be read together. One alone is not enough for a conclusive result.\u003c\/li\u003e\n  \u003cli\u003eThe type of ovarian cancer matters. HRD testing is relevant for high-grade serous, endometrioid, and clear cell carcinomas, and ovarian carcinosarcoma. It is not recommended for low-grade epithelial ovarian carcinoma.\u003c\/li\u003e\n  \u003cli\u003eYou must be able to take oral medication, because all PARP inhibitors are given by mouth.\u003c\/li\u003e\n  \u003cli\u003eTissue quality matters. A sample of at least 5 mm in diameter with at least 30% tumor cells is needed for a reliable result.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe authors conclude that this structured approach is intended to optimize HRD testing, improve clinical decision-making, and ultimately improve patient outcomes.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations and Open Questions\u003c\/h2\u003e\n\u003cp\u003eThe statement openly acknowledges several gaps in current knowledge.\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMissing confidence intervals:\u003c\/strong\u003e the 95% confidence intervals for test cutoffs are generally not reported, so precision around the thresholds is uncertain.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLimited clinical outcome data:\u003c\/strong\u003e many assays lack their own PFS and ideally OS data, because access to clinical trial specimens is limited. Some tests rely on \"bridging\" — agreement with an already-validated test — rather than their own outcome data.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnclear value in recurrent disease:\u003c\/strong\u003e there is a lack of clinical and preclinical trials on HRD testing in recurrent or pretreated ovarian cancer. Alterations in tumor cells and the tumor microenvironment could affect how meaningful the results are.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnclear value after neoadjuvant chemotherapy:\u003c\/strong\u003e the significance of HRD testing on tissue obtained after neoadjuvant chemotherapy at the time of primary diagnosis remains unclear, and tumor necrosis at interval surgery can negatively influence results.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHard cutoffs on a continuous marker:\u003c\/strong\u003e GIS is a continuous measurement, but a fixed cutoff is applied to it. Values near the threshold require interdisciplinary discussion.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThese are the reasons the statement emphasizes interdisciplinary review rather than a single automatic number.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Advice for Patients\u003c\/h2\u003e\n\u003col\u003e\n  \u003cli\u003eAsk for genetic counseling and germline BRCA1\/BRCA2 testing if you have been diagnosed with ovarian cancer. Guidelines recommend this for all patients.\u003c\/li\u003e\n  \u003cli\u003eIf your germline test is negative, ask whether HRD testing is appropriate for you. Ideally this should be done at the same time as germline testing.\u003c\/li\u003e\n  \u003cli\u003eConfirm that your tumor type qualifies for HRD testing — high-grade serous, endometrioid, clear cell, or carcinosarcoma. Low-grade tumors are excluded.\u003c\/li\u003e\n  \u003cli\u003eMake sure your tissue sample is adequate: at least 5 mm in diameter with at least 30% tumor cells. If a lymph node was used, tumor content may be much lower (below 10%) and the result less reliable.\u003c\/li\u003e\n  \u003cli\u003eAsk which specific assay is being used, and whether it has been validated in a clinical trial such as PAOLA-1 with PFS and ideally OS data.\u003c\/li\u003e\n  \u003cli\u003eIf your result falls close to the cutoff, ask for it to be discussed in an interdisciplinary tumor board before a final treatment decision is made.\u003c\/li\u003e\n  \u003cli\u003eIf your disease has recurred after prior PARP inhibitor or immunogenic therapy, discuss with your team whether testing outside a clinical trial is appropriate for you.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is HRD testing and why does it matter for ovarian cancer?\u003c\/h3\u003e\n\u003cp\u003eHRD is a measurable biological signal showing a weakness in a tumor's DNA repair. Testing for it helps doctors identify which patients with advanced ovarian cancer are likely to benefit from PARP inhibitors, a class of oral maintenance drugs given after initial treatment. It is not one uniform test, and the laboratory and timing can affect your treatment options.\u003c\/p\u003e\n\u003ch3\u003eIf my germline BRCA test is positive, do I still need HRD testing?\u003c\/h3\u003e\n\u003cp\u003eNo. If you have a positive germline BRCA1 or BRCA2 mutation, additional HRD testing is considered obsolete because the germline result already answers the question. A positive germline result means you are considered HRD positive and eligible for maintenance therapy with olaparib, so further testing would not change that decision.\u003c\/p\u003e\n\u003ch3\u003eMy germline test was negative. Can HRD testing still help me?\u003c\/h3\u003e\n\u003cp\u003eYes. If germline testing for BRCA1 and BRCA2 is negative, HRD testing can be pursued as a second test in a two-step procedure, immediately after the negative result. It may show whether your tumor has a genomic instability signature that predicts PARP inhibitor benefit. Ideally, HRD testing should be done at the same time as germline testing.\u003c\/p\u003e\n\u003ch3\u003eWhich types of ovarian cancer qualify for HRD testing?\u003c\/h3\u003e\n\u003cp\u003eHRD testing is particularly relevant for high-grade serous, endometrioid, and clear cell epithelial ovarian carcinoma, and ovarian carcinosarcoma, following the WHO classification of 2014. All forms of low-grade epithelial ovarian carcinoma are not eligible for further HRD testing. Your tumor type should be confirmed before testing is arranged.\u003c\/p\u003e\n\u003ch3\u003eWhat tissue sample is needed for a reliable HRD result?\u003c\/h3\u003e\n\u003cp\u003eAn adequate sample should be at least 5 mm in diameter with at least 30% tumor cells. If a lymph node metastasis is used, the tumor cell count can be low because of many immune cells and may fall below 10%, making the result less reliable. If tumor tissue cannot be obtained during surgery, minimally invasive biopsies may be taken.\u003c\/p\u003e\n\u003ch3\u003eWhat does it mean if my HRD result is close to the cutoff?\u003c\/h3\u003e\n\u003cp\u003eResults near the threshold are not always a clear answer. The 95% confidence intervals for test cutoffs are generally not reported, so the precision of each cutoff is uncertain. A result just above or just below the cutoff should be discussed in an interdisciplinary setting among pathologists, gynecologic oncologists, and other specialists, considering your clinical context.\u003c\/p\u003e\n\u003ch3\u003eCan I have HRD testing if my cancer has come back or I already had PARP inhibitors?\u003c\/h3\u003e\n\u003cp\u003eIf your disease has recurred or was previously treated, HRD testing may not be reliable because changes in tumor cells and the tumor microenvironment could affect the significance of results. Patients who already received PARP inhibition or other immunogenic therapy during ovarian cancer treatment should be excluded from testing outside clinical trials. If an HRD test was already done in a recurrence setting, there is no need to reevaluate.\u003c\/p\u003e\n\u003ch3\u003eWhen should a patient with advanced ovarian cancer seek a second opinion about HRD testing and PARP inhibitor maintenance therapy?\u003c\/h3\u003e\n\u003cp\u003eA second opinion is worth considering when the HRD result falls close to the test cutoff, since the 95% confidence intervals for cutoffs are generally not reported and precision around the threshold is uncertain. It also helps when the assay used lacks its own progression-free and overall survival data, when the tissue sample is under 5 mm or below 30% tumor cells, or when testing is proposed for recurrent disease, after neoadjuvant chemotherapy, or for a low-grade tumor, where testing is not recommended. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Intergroup-statement: statement of the german ovarian cancer commission, the North-Eastern German Society of gynecological Oncology (NOGGO), AGO Austria and AGO Swiss regarding the use of homologous repair deficiency (HRD) assays in advanced ovarian cancer.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Chinczewski L, Harter P, Heukamp L, Mayr D, Grimm C, Heinzelmann-Schwarz V, Wimberger P, Mahner S, Braicu IE, Schmitt W, Denkert C, Sehouli J.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e Archives of Gynecology and Obstetrics (2025), volume 311, pages 1445–1450. DOI: 10.1007\/s00404-025-07991-y. Published online 12 March 2025. Received 30 January 2025; accepted 21 February 2025.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eArticle type:\u003c\/strong\u003e Position Statement. Open Access under a Creative Commons Attribution 4.0 International License.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eLead author affiliation:\u003c\/strong\u003e Department for Gynecology, Campus Virchow-Klinikum, Charité–Universitätsmedizin Berlin, Berlin, Germany. Co-authors are affiliated with institutions in Germany (Essen, Hamburg, Munich, Dresden, Marburg), Austria (Vienna), and Switzerland (Basel).\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest disclosure:\u003c\/strong\u003e the statement reports advisory board and honorary relationships with Myriad MyChoice, GSK, ESAI, and NOGGO e.V.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c\/strong\u003e This patient-friendly article is based on peer-reviewed research.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47738988363932,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/es\/products\/hrd-testing-in-advanced-ovarian-cancer-a-patient-guide-to-the-2025-intergroup-statement","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}