Confused by HRD testing? See a webinar, "HRD Testing in Practice," with James Hamrick and Rebecca Arend, hosted by Caris. It's July 15, 2025, at 2 pm pacific.
Find information and registrtion here:
https://carisls.zoom.us/webinar/register/8817491420887/WN_SYOCF243SLiweIgatZj9gg#/registration
See a Linked In invite also, here.
The invitation reads,
- Homologous recombination deficiency (HRD) testing is an increasingly important tool in guiding PARP inhibitor therapy for ovarian cancer, but its interpretation remains complex. In this webinar, Dr. Rebecca Arend will present findings from a new large-scale study of over 1,600 real-world ovarian cancer cases, exploring how genomic scar scoring (GSS) and BRCA1/2 mutation status independently and jointly predict survival.
- The session will also touch on ongoing efforts to harmonize HRD testing methods, highlighting how comprehensive assays may offer improved patient selection. Join us to deepen your understanding of HRD and its evolving role in precision oncology.
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AI CORNER
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I asked Chat GPT for an overview suitable for a new oncology fellow.
Homologous recombination deficiency (HRD) testing is a form of molecular profiling used to identify tumors with impaired ability to repair double-strand DNA breaks through the homologous recombination (HR) repair pathway. This is clinically important because tumors with HRD are particularly sensitive to DNA-damaging agents such as platinum-based chemotherapies and PARP inhibitors. In oncology, HRD testing is most commonly applied in ovarian, breast, prostate, and pancreatic cancers, where it can help guide decisions about using PARP inhibitors like olaparib or niraparib.
The most well-known cause of HRD is a mutation in the BRCA1 or BRCA2 genes. These mutations can be either inherited (germline) or acquired in the tumor (somatic). However, HRD can also result from defects in other genes involved in the homologous recombination pathway, such as RAD51C, RAD51D, and PALB2, or from broader genomic instability that reflects a history of defective repair even if the specific mutation is no longer present.
There are two broad approaches to HRD testing. One type focuses on identifying mutations in specific genes like BRCA1/2, often performed through either blood (germline testing) or tumor tissue (somatic testing). The other type assesses genomic “scars” that indicate underlying HRD, even when no clear mutation is found. These genomic instability assays analyze patterns such as loss of heterozygosity (LOH), telomeric allelic imbalance, and large-scale transitions in the tumor genome. Commercial tests like Myriad’s MyChoice® CDx and Foundation Medicine’s FoundationOne® CDx incorporate such measures to generate an HRD score or LOH score. A high score suggests that the tumor has the characteristic features of HRD and may respond better to therapies that exploit this vulnerability.
In clinical practice, HRD testing is used to identify patients who may benefit from PARP inhibitors beyond just those with BRCA mutations. For example, in ovarian cancer, patients with high HRD scores have shown improved outcomes with maintenance PARP inhibition even if they lack BRCA mutations. However, not all HRD-positive tumors respond to treatment, and some tumors classified as HR-proficient may still benefit. Finally, germline findings in BRCA or other HR pathway genes may have implications for hereditary cancer syndromes, which should prompt genetic counseling and possibly testing of family members.
In short, HRD testing helps oncologists stratify patients based on DNA repair capacity and personalize therapy accordingly, especially in tumors where PARP inhibitors play a key role.
