Friends of Cancer Research (Friends) is excited to announce new data from the Homologous Recombination Deficiency (HRD) Harmonization Project shared this weekend at The Association of Molecular Pathology Annual Meeting. The HRD Harmonization Project is a unique research partnership focused on understanding the variability in HRD assays and developing strategies to align methodology for measuring and using HRD.
HRD is a biomarker with promise in identifying patients with certain cancers who are more likely to benefit from PARP inhibitors and other DNA repair targeting drugs. Assay developers may use different factors to define HRD including loss of heterozygosity (gLOH) and mutations in genes involved in the homologous recombination (HR) repair pathway. It is essential that tests determining HR status provide consistent results for providers and patients.
Our latest findings from the Friends’ HRD Harmonization Project compared outputs from 11 HRD assays that used the same data from an in silico ovarian cancer dataset to measure HR status. Our analysis demonstrates variability in HR status calls across assays. Samples with BRCA1 and BRCA2 mutations were more uniformly called HRD.
“These findings provide an initial step toward understanding the variability in HRD assays and will serve as a foundation for HRD assay alignment and optimal use,” said Dr. Jeff Allen, President & CEO of Friends of Cancer Research. “The medical community needs to set an expectation that regardless of what test patients get, the results are accurate and reliable. This research consortium is an excellent example of work toward that goal.”
Across assays, the average percent of HRD calls out of all of the samples was 44% (median 49%), which is consistent with prior publications. A survey of assay characteristics indicated variability in which factors are included in HRD analysis pipelines across diagnostics developers (e.g., whether they measured gLOH or not), highlighting the importance of finding ways to reach consensus across assays used for clinical decision-making.
Next steps for the project include a similar analysis of the variability in HRD calls across assays with freshly extracted formalin-fixed paraffin-embedded human archival ovarian tumor samples in 2023.
The HRD Harmonization Project is a collaborative effort across multiple sectors aiming to rapidly advance research and improve patient care.
Click to read the latest findings
For updates on this three-phase project visit: https://friendsofcancerresearch.org/hrd/
Partners participating in this project include:
AbbVie, ACT Genomics, Ambry Genetics, Amoy Diagnostics, AstraZeneca, Arizona State University, Bayer, Bionano Genomics, Inc., Bristol Myers Squibb, Caris Life Sciences, DNAnexus, EMD Serono, Inc., European Organisation for Research and Treatment of Cancer (EORTC), U.S. Food and Drug Administration (FDA), Foundation Medicine, Inc., GlaxoSmithKline, Guardant Health, Inc., Illumina, Inc., Invitae, Janssen Pharmaceuticals, MD Anderson Cancer Center, Merck & Co., Inc., Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, Myriad Genetics, National Cancer Institute (NCI), NeoGenomics, Novartis, OmniSeq, PathAI, Personalis, Inc., Personal Genome Diagnostics (PGDx), Pfizer, Inc., Resolution Bioscience, Inc., SOPHiA GENETICS, Tempus Labs, Inc., Thermo Fisher Scientific, University of Alabama at Birmingham, University of Heidelberg.
Co-Authors:
Hillary Stires (Friends of Cancer Research), Zhiwei Zhang (National Cancer Institute), Lisa McShane (National Cancer Institute), Jonathan Bieler (SOPHiA Genetics), Li Chen (Fredrick National Laboratory), Mohit Gupta (Thermo Fisher Scientific), Alexander J. Lazar (MD Anderson Cancer Center), Brittany McKelvey (Friends of Cancer Research), Sarabjot Pabla (OmniSeq), Jerod Parsons (Tempus Labs, Inc.), Daniel Saul (Bionano Genomics, Inc.), Omar Serang (DNAnexus), Ethan S. Sokol (Foundation Medicine, Inc.), Elizabeth Starks (Invitae), Brad Thomas (Neogenomics), Shuang Yang (AmoyDx), Jennifer Yen (Guardant Health, Inc.)., Mark Stewart (Friends of Cancer Research), Jeff Allen (Friends of Cancer Research).
About Friends of Cancer Research
Friends of Cancer Research (Friends) drives collaboration among partners from every healthcare sector to power advances in science, policy and regulation that speed lifesaving treatments to patients. For more information, please visit www.focr.org.
