Recent research led by Prof. Dr. med. Carsten Denkert and Marcel Romey reveals interesting data on systematic analysis of HRD testing in ovarian cancer patients¹

Homologous recombination deficiency (HRD) testing is a critical component of personalized oncology for ovarian cancer patients. The optimal tissue requirements for these molecular assays are not well-defined, leading to a significant number of unsuccessful assays.

In a collaborative effort with hospitals across Germany and Spain, the team of the Institute of Pathology at Philipps-University Marburg conducted a comprehensive study to analyze tissue requirements for HRD testing. The research focused on a systematic analysis of a large group of patients with ovarian cancer that underwent HRD testing.

The study aimed to systematically analyze tumor and tissue parameters for HRD analysis in a large cohort of real-world cancer samples and develop recommendations for pathologists and gynecological oncologists for selecting tissue samples to maximize the success rate of HRD analyses.

Between October 2020 and September 2022, 2702 patient samples were sent to the Institute of Pathology of the Philipps-University Marburg for HRD testing using the Myriad MyChoice CDx Plus assay. Samples with a DNA concentration of at least 1 µg/µl were considered for the laboratory workflow. Molecular profiling was performed by Next-Generation Sequencing (NGS) to analyze mutations in BRCA1, BRCA2, and 13 additional HRR genes. The genomic instability score (GIS) was determined by combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transition (LST) analyses.

Key findings

Out of 2654 processed samples, 2396 (90.3%) were successfully tested. Among these, 984 (41.1%) were HRD positive, and 1412 (58.9%) were HRD negative. A total of 363 (15.2%) samples were BRCA1/2-mutated*. BRCA1/2-mutated samples had significantly higher GIS values than those with wild-type BRCA1/2-status (p<0.0001).

*The frequency of BRCA1/2 mutations found in this cohort was about half the rate presented in the PAOLA-1 cohort. The difference might be explained by germline testing by certain cancer centers beforehand, only sending tumor samples for HRD testing that had shown a wild type germline BRCA1/2 status.

Success rates of up to 98% can be achieved with optimized tissue selection

Tumor cell content ≥30% Tumor area ≥ 0.5 cm²

Tumor cell content, tumor area, and histology significantly affected the probability of successfully analyzing a sample (p<0.0001). By considering this, success rates of up to 98% can be achieved.

Based on these findings, the study recommends selecting patients’ tumor samples with a cell content ≥30% and a tumor area ≥0.5 cm² after hematoxylin and eosin immunohistochemical staining. This ensures optimal chances of success and conclusive results.

Impact on personalized therapeutic strategies

This comprehensive evaluation further contributes to the standardization of recommendations for HRD testing in ovarian cancer. The implications are profound, having a substantial impact on personalized therapeutic strategies for this aggressive tumor type.

We believe that the study’s recommendations serve as a valuable guide for pathologists and gynecological oncologists to enhance the success rate of HRD analyses. This, in turn, opens new opportunities for more patients to benefit from targeted treatments.

For a detailed exploration of the study’s findings, please refer to the full publication¹ or check our clinical summary.

What is MyChoice CDx Plus?

The test employed in this study was MyChoice CDx Plus, that combines tumor BRCA1 and BRCA2 testing along with Genomic Instability Score for the most comprehensive HRD status assessment.

MyChoice is the only HRD test prospectively validated with LoE1A in Phase III studies (PAOLA-1, PRIMA, VELIA)^2,3,4 for use in first-line treatment of ovarian cancer and approved by the FDA as a companion diagnostic. Robust long-term data confirm MyChoice testing improves survival in patients with newly diagnosed advanced ovarian cancer who receive first-line treatment. Results are ready in 2-3 weeks to aid you in making informed treatment decisions in a timely manner for your patients.

How to access MyChoice?

Wondering how to access the gold standard in HRD testing? MyChoice is available through local laboratories in the EU and as a  service provided by Myriad Genetics. Visit our homepage to explore the seamless process of ordering MyChoice  – your key to unlocking precision in oncology. Join the countless healthcare professionals who rely on MyChoice for accurate and comprehensive genomic insights.

MyChoice is provided by Myriad Genetics, committed to improving timely access to genomic insights, through local testing, education and partnerships.

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References

1. Romey M. et al. Systematic analysis of HRD testing in ovarian cancer – development of recommendations for optimal assay performance. Modern Pathology 2024
2. Ray-Coquard I. et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Annals of Oncology 2023
3. Gonzalez-Martin, A. et al. Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. European Journal of Cancer 2023
4. Coleman, R. L. et al. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. New England Journal of Medicine, 2019