Homologous Recombination Deficiency (HRD) Testing: Frequently Asked Questions
Summary: This resource answers frequently asked questions about the different biomarkers included in HRD testing.
By Clinical Education at JAX | January 2024
What is HRD?
Homologous recombination deficiency is the result of a dysfunctional DNA repair process known as homologous recombination repair (HRR). HRR is responsible for repairing DNA double-strand breaks. The HRR protein complex includes BRCA1, BRCA2, RAD51, PALB2, BARD1, and others (Figure 1). When genes involved in HRR, mainly BRCA1/2, develop mutations, the DNA repair process is inhibited, leading to wide-spread chromosomal structural changes across the cell. This accumulation of chromosomal variants is also known as genomic instability.
Figure 1: Homologous recombination repair.
What is included in HRD testing?
Multiple biomarkers can be used to assess HRD, but there is no consensus about which biomarkers are the best indicators of HRD. Labs determine which biomarkers to include on the tests independently. In general, HRD tests assess the cause of HRD (pathogenic variants in BRCA1/2) or the effect of HRD (genomic instability) (Figure 2).
Figure 2: Biomarkers included in HRD testing
What is the difference between HRD and an HRD score?
HRD is the presence of a dysfunctional homologous recombination repair (HRR) pathway. An HRD score is a proprietary lab-specific algorithm based on one or multiple HRD biomarkers.
What is the difference between LOH and an HRD score?
Loss of Heterozygosity (LOH) is one of many biomarkers that assess the effect of HRD. LOH is a measure of genomic instability that results from the loss of one copy of a gene or chromosomal region. HRD score can include LOH, but this will vary from lab to lab.
How does HRD testing vary between labs?
Some testing labs only assess BRCA1/2 gene variants. Other labs will also include genomic instability scores, such as LOH or HRD.
What is the benefit of HRD testing?
For certain cancer types (e.g., ovarian), identifying a cancer with HRD can help guide treatment decisions, especially in the selection of therapies such as PARP inhibitors (PARPi). PARPi are known to be effective in some cancers with HRD. Use of PARPi in the setting of HRD further inhibits DNA repair, leading to cell death of the cancer cells and, potentially, improved patient outcomes.
PARP inhibitors are approved for use in some BRCA-positive ovarian, breast, pancreatic, and prostate cancers. See PARPi Inhibitors: Overview and Indications for more information about the benefit of PARPi in different scenarios.
How is HRD status reported?
HRD results are reported differently among laboratories, depending on the biomarkers used in testing. HRD may be reported as positive or negative, or individual HRD biomarkers may be reported separately, such as the presence of BRCA1/2 variants or LOH score.
Where can I get help with HRD test results?
Details of test parameters are often available within the test report, on the laboratory website, or upon request from the lab representative. Genomic tumor boards and consultation with genetics professionals can be useful sources of peer consultation. Referral to appropriate specialists, like a genetic counselor, may be considered with suspected germline findings.
Learn More
PARP Inhibitors: Overview and Indications. Discusses FDA-approved indications for PARPi for maintenance therapy and cancer treatment.
Exploring Cancer Biomarker Testing (CME|CNE). Learn about benefits, limitations, and challenges of using cancer biomarker testing.
Interpreting Cancer Biomarker Testing – When is Additional Testing Needed? (CME|CNE). Learn when additional cancer biomarker testing is indicated for further evaluation of genome-informed therapy.
Indications for Germline Testing after Genomic Tumor Testing (CME|CNE). Identifies genetic red flags to inform personal and family history risk assessment and genomic tumor test results that are suggestive of a germline variant.
References
Mangogna A, Munari G, Pepe F, et al. Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches. J Pers Med. 2023 Feb 2;13(2):284.
Disclaimer
All information in this resource is provided for educational purposes only.