What is HRD Status in Ovarian Cancer?

Being “HRD positive” means your ovarian cancer cells have a specific flaw: they have lost their primary ability to accurately repair their own DNA when it gets damaged ^[1]. HRD stands for Homologous Recombination Deficiency. This weakness is a crucial piece of information for your care team, because it makes the cancer highly vulnerable to a class of targeted drugs called PARP inhibitors ^[2]. Knowing your HRD status helps determine if these drugs are the right next step for your treatment ^[3].

The Two-Mechanic Analogy

To understand why HRD matters, it helps to think of a cancer cell as a machine that constantly needs maintenance. Every time a cell divides, its DNA can sustain damage.

A healthy cell relies on its primary mechanic—a highly accurate DNA repair system called Homologous Recombination (HR) ^[4]. When a tumor is HRD positive, it means this primary mechanic is missing or on strike ^[1].

To survive, the cancer cell is forced to rely on its backup mechanic—a different repair system managed by a protein called PARP ^[5]. This backup system is error-prone, but it keeps the cancer cell alive.

This is where PARP inhibitors come in. These drugs are designed to block the backup mechanic ^[6]. When an HRD-positive cancer cell is treated with a PARP inhibitor, it loses both of its repair systems. The main mechanic was already missing, and the drug disables the backup. Without any way to fix its DNA, the damage becomes catastrophic, and the cancer cell dies ^[7]. In medicine, exploiting this dual weakness is called synthetic lethality ^[6].

How Does a Tumor Become HRD Positive?

Your doctor determines your HRD status by testing a sample of your tumor tissue. It is important to know that this tumor testing (somatic testing) looks at the genetics of the cancer itself, which is different from a blood test looking for inherited (germline) mutations passed down in your family ^[8].

A tumor usually becomes HRD positive in one of two ways:

• BRCA Mutations: The BRCA1 and BRCA2 genes are the instruction manuals for the primary HR mechanic. If you have a mutation in one of these genes, your tumor is almost certainly HRD positive ^[8].
• Other Causes (BRCA-Wildtype): You can still be HRD positive even if your BRCA genes are perfectly normal (referred to as BRCA-wildtype) ^[9]. Other genes involved in DNA repair (such as RAD51C or BRIP1) can malfunction, causing the exact same repair deficiency ^[10].

When the lab tests your tumor, they often look for genomic scars ^[11]. Because the cancer cell has been using its sloppy backup repair system, its DNA becomes patched together haphazardly ^[9]. The lab measures this messiness and calculates an HRD score.

(Note: Different testing companies use different scoring methods. For example, the Myriad myChoice CDx test uses a score out of 100, where 42 or higher is officially HRD positive ^[12][13]. However, other tests like FoundationOne CDx look at the percentage of scarring, called LOH percentage ^[14]. If you see a low number on your report, check which test was used before assuming you are HRD negative).

What HRD Means for Your Treatment Options

If your tumor is HRD positive, it dramatically shifts your treatment landscape.

First, HRD-positive tumors tend to be very sensitive to standard platinum-based chemotherapy ^[15]. Because chemotherapy works by damaging cancer cell DNA, the tumor struggles to recover from the treatment.

Second, an HRD-positive status makes you a strong candidate for a PARP inhibitor (such as olaparib, niraparib, or rucaparib) ^[3][16]. These are usually given as maintenance therapy—a daily pill you take after finishing your initial rounds of chemotherapy ^[17]. The goal of maintenance therapy is to delay or prevent the cancer from returning by wiping out any lingering cancer cells ^[2]. Depending on your specific situation, patients typically take these maintenance medications for 2 to 3 years, though your doctor will tailor this to you.

While clinical trials show that patients with HRD-positive tumors derive a significant clinical benefit—experiencing a much longer period of time without the cancer growing compared to those with HRD-negative tumors ^[18][17]—it is not a magic pill. PARP inhibitors can cause side effects like fatigue, nausea, and changes in your blood counts (such as anemia), meaning you will need regular blood tests and monitoring by your care team ^[2].

What if I am HRD negative?

If your tumor is HRD negative, you still have options. While PARP inhibitors may offer less benefit, your doctor might recommend other maintenance strategies, such as targeted therapies that limit blood flow to the tumor (like bevacizumab), or clinical trials exploring new drug combinations ^[19].