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Review
. 2025 Aug;27(8):685-704.
doi: 10.1016/j.jmoldx.2025.05.003. Epub 2025 Jun 13.

Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists

Susan J Hsiao  1 , Destin Black  2 , Kelly A Devereaux  3 , Ian S Hagemann  4 , Lawrence J Jennings  5 , Diana Mandelker  3 , Vera A Paulson  6 , Michelle Shiller  7 , Tracy L Stockley  8 , Eric Vail  9 , Praveen Vikas  10 , Anna Yemelyanova  11
Affiliations
Review

Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists

Susan J Hsiao et al. J Mol Diagn. 2025 Aug.

Abstract

Homologous recombination deficiency (HRD) is a genomic feature present in some malignant neoplasms and is attributed to the failure of the homologous recombination repair pathway. Tumors with an HRD-positive status may have a distinct prognosis and/or response to therapies, including poly (ADP-ribose) polymerase inhibitors. The Association for Molecular Pathology assembled an expert panel to examine current practice and perform a scoping review of the medical literature pertaining to the molecular detection of HRD in the clinical setting. The expert panel examined the following topics: components of existing and proposed HRD and genomic instability biomarkers (including mutational signatures, loss of heterozygosity, mutations in homologous recombination repair-associated genes, and epigenetic silencing of RAD51C, BRCA1, or BRCA2); technical considerations for identifying genomic scars from tumor and germline next-generation sequencing results; guidelines on interpretation and caveats when reporting assessments of genomic instability and HRD scores; and the clinical significance of HRD. The panel formulated a set of expert consensus opinion recommendations regarding HRD assay design and validation to guide laboratories in developing HRD tests to ensure high-quality and reproducible results.

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Conflict of interest statement

Disclosure Statement To provide active management of potential perceived and/or actual conflicts of interest, a Working Group chair without relevant conflicts was appointed and conflict of interest disclosures were requested from and/or provided by all authors throughout all phases of the consensus manuscript development process. S.J.H. received honorarium from AstraZeneca, receives royalties from Pillar Biosciences, is a member of the CSLI Expert Panel on Molecular Methods, is a member of Clinical Laboratory Improvements Advisory Committee's Next Generation Sequencing Work Group, is a member of the College of American Pathologists' Molecular Oncology Committee, and is a member of the Association for Diagnostics and Laboratory Medicine's Nominating Committee. K.A.D. became a full-time employee for Merck & Co, Inc. (Rahway, NJ) in 2022 and receives stock options. I.S.H. previously received consulting fees from Change Healthcare, receives advisory board honoraria from AstraZeneca and continuing medical education development honoraria from the American Society for Clinical Oncology, PRIME Inc., and the Association for Molecular Pathology, and is a member of the College of American Pathologists' Molecular Oncology Committee. D.M. has received speaker and consulting fees from Astra Zeneca. V.A.P. previously received salary support from evicore; and has held several leadership positions in the molecular pathology division of the Association for Diagnostics and Laboratory Medicine (formerly American Association for Clinical Chemistry). M.S. is an employee at PathGroup Genomic and Molecular Pathology Services; has received speaker fees from Astra Zeneca, Merck, Amgen, Takeda, BMS, Bayer, and GSK; and serves on the advisory boards for Astra Zeneca, Merck, Amgen, Abbvie, and Pfizer. T.L.S. received research funding and consulting fees from Astra Zeneca, is a member of the College of American Pathologists' Molecular Oncology Committee, and is a member of the European Molecular Genetics Quality Network's Strategic and Scientific Advisory Board. E.V. is a member of the College of American Pathologists' Molecular Oncology Committee, has employment and stock at LunglifeAI, and receives speaker and consulting fees from Bayer, Eli-Lilly, Janssen, Sanofi, Pfizer, PierianDx, Tempus, Caris, Illumina, and Thermo-Fisher Scientific. A.Y. is a member of the College of American Pathologists' Molecular Oncology Committee and Genomic Medicine Committee; received consulting fees from Verastem, Inc.; and received speaker fees from the Association of Cancer Care Centers.

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