What Does HRD-Positive Mean?

This page is for people whose tumor test report says HRD-positive or HRD-negative, most often with ovarian cancer. It explains what the result means, how it is scored, and how it can affect treatment.

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 has trouble fixing DNA damage.

The test described by the FDA does not look only at one gene. It also measures genomic instability across the tumor's DNA. A result of HRD-positive means the tumor has a harmful BRCA1 or BRCA2 mutation, a high enough genomic instability score, or both. A tumor can be HRD-positive from the score alone, without a BRCA mutation. HRD-negative means neither was found.

One FDA-reviewed test, Myriad's myChoice CDx, uses tumor tissue from ovarian cancer. It combines 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 score from an algorithm that measures three things across the genome: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions.

A tumor counts as HRD-positive in either of two cases:

• it carries a harmful BRCA1 or BRCA2 mutation, or
• its Genomic Instability Score is above the test's set threshold.

The cutoff is set by the test. Your report will say which result counted.

The FDA document for the myChoice CDx test covers ovarian cancer, including fallopian tube and primary peritoneal cancer. This page does not cover HRD testing in other cancers. If your report is for another cancer type, ask your oncologist what the result means for you.

The National Cancer Institute notes that cancer cells with BRCA mutations or certain other gene mutations cannot use a key DNA repair process. Olaparib is a PARP inhibitor, a drug that targets a repair process in cancer cells.

For ovarian, fallopian tube, or primary peritoneal cancer, NCI lists olaparib as maintenance therapy. That means it is used after a complete or partial response to platinum chemotherapy. NCI also lists olaparib with bevacizumab as first maintenance therapy for advanced cancer with genomic instability. The FDA document says people with a positive GIS status or BRCA1 or BRCA2 variants showed improved progression-free survival with a PARP inhibitor in the trial it describes. 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. The test described here is run on tumor tissue. It is not the same as a test of your inherited genes. A tumor BRCA result does not by itself tell you whether a mutation is inherited. Ask your doctor whether separate genetic testing makes sense for you or your family.

• 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, what other options are 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, so the result is ready when your team makes those decisions.

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