Homologous recombination deficiency (HRD) testing for ovarian cancer looks at how your body repairs broken DNA strands, which can be associated with this cancer. This testing helps gauge cancer outcomes and guide treatment.
While many factors are thought to contribute to ovarian cancer, changes to your DNA can play an important role.
Inherited and acquired genetic mutations can lead to the development of cancer. In ovarian cancer, mutations in the BRCA1 and BRCA2 genes are known to increase the chances of developing ovarian and breast cancers.
HRD testing looks for damage to these genes, providing a way to predict the likelihood of advanced or high grade serous ovarian cancer (HGSOC).
Your body can repair damaged DNA. It does this through multiple complex mechanisms, including the homologous recombination repair (HRR) pathway.
The HRR pathway uses copies of your genes to repair them, like an engineer looking at schematics.
When the HRR pathway fails, it results in HRD. The presence of HRD means your DNA is not being repaired accurately. Over time, mutations in DNA become genomic scars, patterns of inaccuracy that are replicated in new cells.
These mutations can drive the formation and progression of cancer.
Mutations specific to certain genes, such as BRCA1 and BRCA2, have been linked to ovarian cancer. HRD testing screens these genes to determine how well the HRR pathway is functioning. It then generates an HRD score, which doctors can use to assess ovarian cancer progression.
In this way, HRD is a biomarker — a measurable biological feature that helps determine disease development.
HRD testing typically occurs during or after a diagnosis of ovarian cancer.
HGSOC has a high mortality rate and is rarely detected in its earlier stages. It’s also the most common form of epithelial ovarian carcinoma, the type of tumor responsible for as many as
In addition, HRD-positive tumors respond well to treatment with poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) and platinum-based chemotherapy. This kind of testing enables your care team to identify you as a candidate for this treatment and start the treatment as soon as possible.
To perform HRD testing for ovarian cancer, healthcare professionals will use a tissue sample obtained through somatic testing, or tumor testing. Your doctor will recommend surgery or biopsy as options, based on your individual needs.
Your tissue sample will be evaluated for genetic mutations and genomic scars that indicate the severity of errors in the HRR pathway.
Specifically, HRD testing for ovarian cancer
- Large-scale transitions (LST): breaks in chromosomes that leave behind large fragments, a sign of chromosomal instability
- Loss of heterozygosity (gLOH): the irreversible loss of an allele, one of two copies of a gene acquired from your parents, at a specific chromosome site
- The number of telemetric imbalances (TAI): the number of chromosome sites that are experiencing unbalanced allele expression
HRD testing is often paired with germline testing, a less invasive genetic screening method.
Germline testing can be done using blood, saliva, or cheek swabs. It specifically looks for inherited genetic mutations that increase susceptibility to certain cancers.
Germline testing can determine whether you’ve inherited BRCA1 and BRCA2 mutations, for example, while HRD screening for ovarian cancer can determine how severely HRR pathway function is affected.
When combined, these ovarian cancer screening methods provide important insights into overall outlook, familial risk, and which therapies may be the most beneficial.
Your HRD testing score is determined by the combined outcomes of your LST, gLOH, and TAI tests.
An HRD score of
You may still be a candidate for PARP inhibitor treatment if your HRD rating is below 42 and you test positive for BRCA mutations.
Your doctor will discuss what your HRD rating means and how it relates to the presence of BRCA mutations.
Genetic testing cannot universally detect ovarian cancer. Even within genetic testing, not every genomic scar can be found using the same screening methods.
To look for additional genomic factors, a genetic counselor may recommend other screening tools, such as:
- folate receptor-alpha (FR-alpha) testing
- NTRK genetic screening
- microsatellite instability (MSI) testing
These tests evaluate protein expression changes that may indicate genetic mutations specific to ovarian cancer.
There is no universal screening protocol for ovarian cancer. Your healthcare team will determine whether and when to screen you for ovarian cancer based on your symptoms, family history, and other risk factors.
Traditional ovarian cancer tests still play an important role in detection and diagnosis.
Your doctor may recommend diagnostic imaging such as:
- computed tomography (CT)
- magnetic resonance imaging (MRI)
- positron emission tomography (PET)
These tools help visually identify abnormal tissue growth on your ovaries. They can also help determine whether ovarian cancer has spread to nearby areas of your body.
In addition to diagnostic imaging, other procedures can help healthcare professionals assess the stage of cancer or obtain tissue samples, including:
Any ovarian cancer test may be paired with blood work.
Blood tests check for the biomarkers of other tumor types and systemic changes from cancer that appear as abnormal hormone levels or out-of-range blood cell counts.
HRD testing for ovarian cancer tells your doctor whether your HRR pathway is working as it should. When your HRR pathway fails, damage to your DNA is repaired incorrectly, resulting in mutations that can encourage cancer development.
While not all ovarian cancers test positive for HRD, this biomarker is considered an accurate predictor of advanced ovarian cancer and HGSOC.
HRD testing lets your doctor know whether you could benefit from certain targeted therapies. This will allow you to start those treatments as soon as possible.