What Does HRD-Positive Mean?

HRD stands for homologous recombination deficiency. Homologous recombination is one of the main ways healthy cells repair broken DNA. When this repair system fails in a cancer cell, the cell falls back on sloppier repair methods. Those backup methods leave behind a distinctive pattern of scrambled DNA across the genome.

An HRD test usually does not look for one single gene. Instead, it scans the tumor's entire set of DNA for that scrambled pattern, sometimes called a "genomic scar." A result of HRD-positive means the tumor shows this pattern. This can happen with or without a BRCA1 or BRCA2 mutation. HRD-negative means the tumor does not show enough of this pattern.

Widely used tests, such as Myriad's myChoice CDx, combine two pieces of information into one report.

• BRCA1 and BRCA2 status. Whether the tumor carries a harmful mutation in either gene.
• Genomic Instability Score (GIS). A single number built from three measures of DNA damage across the genome: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions.

A tumor counts as HRD-positive in two cases. First, if it carries a harmful BRCA1 or BRCA2 mutation. Second, if its Genomic Instability Score meets or crosses the test's threshold. In the FDA technical information for this test, that threshold is a score of 42 or higher. A tumor without a BRCA mutation and with a lower score is HRD-negative.

HRD testing is used most often in high-grade serous ovarian cancer. There, it is now a standard part of planning treatment. It is also used more and more in some breast, prostate, and pancreatic cancers. In these cancers, PARP inhibitor drugs are being studied or approved for specific situations.

Cells with homologous recombination deficiency depend heavily on a backup repair enzyme called PARP to survive. A class of drugs called PARP inhibitors, including olaparib and niraparib, blocks that backup system. In a cell that already lacks its main repair pathway, blocking the backup too can kill the cancer cell. Healthy cells, which still have working repair systems, are largely spared. This approach is called synthetic lethality.

In ovarian cancer, doctors often add a PARP inhibitor after chemotherapy works well. This is called maintenance therapy, and it aims to delay the cancer's return. This option is usually offered to people whose tumors are HRD-positive. In large trials, people with HRD-positive tumors on olaparib-based maintenance had much longer progression-free survival. This was compared with standard maintenance that skipped a PARP inhibitor. People with HRD-negative tumors can still benefit from PARP inhibitors, but the effect is usually smaller. Your team weighs the result alongside other factors.

HRD-positive does not tell you your stage. It does not predict exactly how long treatment will work for you. It does not mean you inherited a cancer-related gene mutation. HRD can come from an inherited BRCA mutation, from a BRCA mutation that arose only in the tumor, or from damage unrelated to BRCA. Because of this, an HRD-positive tumor result differs from a genetic test that shows an inherited risk gene. It does not by itself tell your family members anything about their own risk. If a BRCA mutation is found, your doctor may suggest a separate germline genetic test on blood or saliva. That test checks whether the mutation is inherited.

• Was my BRCA status tested along with my HRD score, and what did each result show?
• Does this result make me eligible for a PARP inhibitor, and at what point in treatment?
• If I am HRD-negative, are there other maintenance options being considered?
• Should I also have germline genetic testing to check whether a mutation is inherited?

An HRD result is not an emergency finding. It typically becomes relevant after initial treatment, when your care team decides on maintenance therapy. Still, ask about it early, since timing can matter. PARP inhibitor maintenance is usually started within a set window after chemotherapy ends.

• FDA — myChoice CDx Technical Information (PMA P190014, Supplement S003)
• National Cancer Institute — Olaparib