What is HRD Status?

When homologous recombination is not able to fix damaged DNA, this is called homologous recombination deficiency (HRD). Approximately 50% of all ovarian cancer tumors have homologous recombination deficiency, or are considered HRD+. Your patient’s HRD status will be determined one of two ways, first by analyzing for a change in their BRCA1 and BRCA2 genes, and second through a specialized tool known as genomic instability (GI).

Homologous Recombination Deficiency (HRD)

is present in approximately 48%1 of ovarian cancer tumors

Patients with ovarian cancer

Some Causes of HRD are well established while others remain unknown2,3,4

There are limitations to determining HRD status when evaluating each cause individually

HRD resulting from epigenetic events such as BRCA1 promoter methylation will be missed with a gene squencing approach5,6

HR pathway gene mutations other than BRCA1 and BRCA2 are rare and it is unclear if they are connected to HRD7,8


identifies more ovarian cancer tumors with HRD than other testing methods1

Patients with ovarian cancer

There are many ways HRD can be Evaluated

A study was done on 3,278 ovarian tumors comparing 2 methods,
Genomic Instability Status (GIS) and %LOH9

  • Commercial ovarian sample data from myChoice®CDx laboratory
  • Myriad reconstruction algorithm used to reconstruct genome profiles
  • myChoice®CDx calculated using standard methods
  • Published method used to calculate % LOH score
  • Comparisons were performed between myChoice®CDx and %LOH for the entire cohort, BRACm only, and BRACAwt only samples

myChoice® CDx

myChoice® CDx identifies ~34% more tumors with HRD than %LOH alone

CDx vs. %LOH1

Approximately 24% of all ovarian cancer is hereditary.

Per national guidelines, all ovarian cancer patients are eligible for genetic testing.

myChoice®CDx can inform early -line treatment decisions with LYNPARZA® (olaparib) and late-line treatment decisions with Zejula® (niraparib)

  1. Moore et al. Lancet Oncol 2019
  2. Bonadio et al. Clinics 2018
  3. Watkins et al. Breast Ca Res 2014
  4. Panagiotis et al. Cancer Discov 2015
  5. Timms et al. Br Ca Res 20142.
  6. Baldwin et al. Cancer Research 20003.
  7. Norquist et al. JAMA Oncol. 20164.
  8. The Cancer Genome Atlas. Nature 2011
  9. Mills et al. Presentation for 2020 SGO Annual Meeting. SGO Annual Meeting on Women’s Cancer (Abstract 1).

myChoice® CDx Intended Use

Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens.

The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status, who are eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may become eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with the targeted therapy listed in Table 1 in accordance with the approved therapeutic product labeling.

Table 1: Companion diagnostic indications

Tumor TypeBiomarkerTherapy
Ovarian CancerMyriad HRD (defined as deleterious or suspected deleterious mutations in BRCA1 and BRCA2 genes and/or positive Genomic Instability Score)Lynparza® (olaparib)
Zejula® (niraparib)

Detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive Genomic Instability Score in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, Inc., a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

* A companion diagnostic is not a requirement for all uses for Zejula. Questions regarding Zejula should be directed to its manufacturer, GSK.