An HRD test is a genomic test that checks whether a tumor has a specific DNA repair weakness called homologous recombination deficiency. When cancer cells lose their ability to fix certain types of DNA damage, they become more vulnerable to targeted therapies, particularly a class of drugs called PARP inhibitors. HRD testing helps oncologists determine which patients are most likely to benefit from these treatments, and it’s most commonly used in ovarian cancer, though its role is expanding to breast, prostate, and pancreatic cancers.
How Homologous Recombination Works
Your cells constantly deal with breaks in their DNA. One of the most dangerous types is a double-strand break, where both sides of the DNA helix snap apart. Healthy cells have a precise repair system called homologous recombination (HR) that fixes these breaks using an intact copy of the DNA as a template. It’s the most accurate repair method your cells have.
When the genes responsible for this repair system are damaged or silenced, cells lose that precision tool. They’re forced to rely on messier, error-prone backup methods to patch DNA breaks. This leads to a buildup of genetic errors and genomic instability, which is what drives cancer growth. Paradoxically, this same weakness can be exploited by treatments that overwhelm cancer cells with DNA damage they can no longer fix.
What the Test Actually Measures
HRD testing typically looks at two things: specific gene mutations and a broader genomic instability score.
The gene mutation component checks for changes in BRCA1, BRCA2, and sometimes other genes involved in the HR repair pathway. BRCA mutations are the most well-known cause of homologous recombination deficiency, but they account for only about half of all HRD-positive tumors. Many tumors have a faulty repair system without carrying a BRCA mutation at all.
That’s where the genomic instability score comes in. This part of the test analyzes the tumor’s DNA for patterns of scarring that accumulate when the HR pathway isn’t working. Three specific types of chromosomal damage are measured:
- Loss of heterozygosity (LOH): stretches of DNA where one copy of a gene region has been lost entirely
- Telomeric allelic imbalance (TAI): uneven DNA at the ends of chromosomes
- Large-scale state transitions (LST): breaks between large segments of chromosomes
These three markers are combined into a single score. A score at or above a specific cutoff (typically 42 or higher on the most widely used platform) indicates the tumor is HRD-positive, meaning homologous recombination is likely not functioning properly. The tumor is considered HRD-positive if it has either a BRCA mutation, a high genomic instability score, or both.
How the Test Is Performed
HRD testing requires a sample of tumor tissue, usually obtained during a biopsy or surgery. The tissue is sent to a specialized lab where DNA is extracted and analyzed using next-generation sequencing technology. Results typically take two to four weeks.
The most commonly used commercial test is the Myriad myChoice CDx assay, which is FDA-approved as a companion diagnostic for certain PARP inhibitor therapies. Other testing platforms exist, including Foundation Medicine’s FoundationOne CDx, and some academic medical centers have developed their own in-house assays. These different platforms don’t always produce identical results, which is an ongoing challenge in the field.
One important limitation: HRD testing captures a snapshot of the tumor’s history. The genomic scars it detects are permanent marks left by past HR deficiency. In some cases, a tumor may have restored its repair function by the time of testing but still carry those scars. This means a positive score doesn’t always guarantee the tumor is currently HR-deficient, which can occasionally affect treatment response.
Why HRD Status Matters for Treatment
The primary reason oncologists order HRD testing is to guide decisions about PARP inhibitor therapy. PARP is a protein your cells use in a separate, simpler DNA repair pathway. PARP inhibitors block this backup repair route. In cells that already lack homologous recombination, blocking PARP too creates a situation where DNA damage piles up with no way to fix it, causing the cancer cells to die. This “double hit” strategy is called synthetic lethality.
In ovarian cancer, where HRD testing has the strongest evidence base, patients with HRD-positive tumors show significantly better responses to PARP inhibitors compared to those with HRD-negative tumors. Clinical trials have demonstrated that HRD-positive ovarian cancer patients treated with PARP inhibitors as maintenance therapy after chemotherapy can experience substantially longer periods before their cancer progresses. The benefit is greatest in patients with BRCA mutations, followed by those who are HRD-positive without a BRCA mutation.
HRD-positive tumors also tend to be more sensitive to platinum-based chemotherapy, which works by creating DNA damage that HR-deficient cells struggle to repair. So even beyond PARP inhibitors, knowing a tumor’s HRD status provides useful information about likely chemotherapy response.
Which Cancers Are Tested
Ovarian cancer is where HRD testing is most established and most commonly ordered. Current treatment guidelines recommend HRD testing for all women diagnosed with advanced epithelial ovarian cancer to help determine maintenance therapy options after initial chemotherapy.
In breast cancer, BRCA testing is standard for guiding PARP inhibitor use, but the broader genomic instability score is not yet as routinely applied. The same is true for prostate and pancreatic cancers, where BRCA and other HR gene mutations matter for treatment decisions, but the composite HRD score hasn’t been validated as thoroughly in clinical trials for these tumor types. Testing practices are evolving as more data becomes available.
Understanding Your Results
An HRD test result will generally classify a tumor into one of three categories. BRCA-mutated means a mutation was found in BRCA1 or BRCA2, which automatically qualifies as HRD-positive regardless of the genomic instability score. HRD-positive/BRCA-wild-type means no BRCA mutation was found, but the genomic instability score is high, indicating the repair pathway is compromised through some other mechanism. HRD-negative means no BRCA mutation was detected and the instability score falls below the threshold.
Being HRD-negative doesn’t mean targeted therapies are off the table entirely, but it does suggest a lower likelihood of benefiting from PARP inhibitors as a single strategy. Some HRD-negative patients still respond to these drugs, and researchers are actively working on combination approaches to extend benefits to this group. Conversely, being HRD-positive is encouraging but not a guarantee of treatment success, since tumors can develop resistance mechanisms over time.
If you’ve been told an HRD test has been ordered for your tumor, it’s worth knowing that this is a standard part of treatment planning for several cancer types. The results will help your oncologist narrow down which therapies give you the best chance of a strong, durable response.