myChoice HRD includes Tumor BRACAnalysis® for an assessment of both tumor BRCA1 and BRCA2 status as well as the tumor’s Genomic Instability Status, evaluated by three biomarkers associated with homologous recombination deficiency (HRD): LOH (loss of heterozygosity), LST (large-scale state transitions), and TAI (telomeric allelic imbalance). myChoice HRD identifies patients that are most likely to benefit from PARP inhibitors. Every patient’s cancer is unique, so their treatment should be as well. Myriad’s myChoice HRD helps physicians select the most effective treatment for their patients, minimizing the time and toxicity associated with ineffective therapies.1-5
myChoice HRD includes Tumor BRACAnalysis® for an assessment of both tumor BRCA1 and BRCA2 status as well as the Genomic Instability Status, which assesses three biomarkers associated with homologous recombination deficiency (HRD). A patient’s tumor is HR deficient when a BRCA1 or BRCA2 mutation is identified and/or Genomic Instability Status is positive. A patient’s tumor has a functioning HR pathway (i.e., is HR proficient) when the tumor BRCA1/2 status and genomic instability are BOTH negative.
The homologous recombination (HR) pathway is reliant on the BRCA1/2 genes. Mutations in these two genes are associated with HRD. Testing for tumor BRCA1/2 genes is one way to determine HRD status and identifies ~2x more patients than germline BRCA1/2 testing alone. myChoice HRD includes Tumor BRACAnalysis to accurately predict HRD status and identify more patients who may benefit from PARP inhibitors than other biomarker assays.
Genomic Instability Status (LOH, TAI, LST)
Genomic Instability Status
The myChoice HRD Genomic Instability Status is another measure of homologous recombination deficiency and is the total sum of LOH (loss of heterozygosity), LST (large-scale state transitions), and TAI (telomeric allelic imbalance). By measuring all three biomarkers of HRD, myChoice HRD may provide more accurate results than measuring LOH alone.6,7,8
Each biomarker is a measurement of genomic instability that results from defects in the homologous recombination pathway.
myChoice HRD Status
myChoice® HRD includes Tumor BRACAnalysis® for an assessment of both tumor BRCA1 and BRCA2 status as well as the Genomic Instability Status, which is three biomarkers associated with homologous recombination deficiency (HRD) to provide the most comprehensive HRD test results.
|Genomic Instablility Status||Tumor BRACAnalysis Status||myChoice® HRD Result|
myChoice HRD Testing identifies 2x as many patients as tumor BRCA testing and 3.5x as many as germline BRCA testing
One approach is to focus on the cause of homologous recombination deficiency by sequencing the genes in the HR pathway (a “genotypic” approach). However, this approach is unable to account for other causes of HRD, both known (such as promoter methylation) and unknown. In addition, it is unclear which mutations in the HR pathway actually lead to HRD and thus, a patient with a gene mutation in a gene other than BRCA may not respond to PARP inhibitors.
Another approach is to look for certain tumor features that are characteristic of homologous recombination deficiency (a “phenotypic” approach). To reliably identify HRD, it is important to assess several different tumor characteristics, including loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).6,7,8 The myChoice HRD assay measures these three different biomarkers of HRD in tumor tissue as well as comprehensive tumor BRCA1/2 analysis to determine a patient’s myChoice HRD result.11,12 By assessing three biomarkers rather than one, Myriad myChoice HRD is the MOST discriminating assessment of a tumor’s HRD status to help optimize treatment decisions.13
These biomarkers are important measurements used to identify tumors with HRD. Testing for the effects of HRD, rather than the cause, will identify more patients whose tumor has HRD. The Genomic Instability Status is derived from an algorithmic measurement of each individual biomarker, which are then added together.6,7,8,11,12
Ovarian Cancer Publications
Studies such as Study 19, ARIEL2 and NOVA demonstrated that an assessment of HRD in addition to BRCA1/2 status can be a predictor of increased efficacy with PARP inhibitor therapy. Explore our publications to learn more about how BRCA1/2 and HRD testing can impact treatment decisions related to PARP inhibitor therapy and DNA-damaging chemotherapy in ovarian cancer.
Tumor BRACAnalysis testing will identify both germline and somatic mutations
Tumor BRCA testing will detect somatic (isolated to the tumor) and germline (in every cell of the body) BRCA1/2 mutations to inform PARP inhibitor treatment decision making. In order to accurately determine whether a BRCA1/2 mutation identified on tumor testing is germline or somatic, follow up hereditary cancer testing on a blood or saliva/buccal sample should be considered.
Myriad provides a comprehensive suite of solutions
Myriad is committed to providing information so that you can confidently determine the best treatment options and manage future cancer risks for your patients.
Inform Treatment Decisions
myChoice HRD is a tumor test that can be used to guide important PARP inhibitor treatment decisions. By testing for BRCA1/2 status and Genomic Instability Status, which evaluates three downstream biomarkers associated with homologous recombination deficiency (HRD), myChoice HRD is capable of identifying more appropriate patients for PARP inhibitors than other biomarker assays.
Inform Treatment Decisions
Myriad myRisk® Hereditary Cancer is a multi-gene germline panel that analyzes clinically-significant genes across a number of hereditary cancer syndromes, with a focus on eight primary cancer sites. This test can accurately determine germline status and inform future cancer risks for patients and their family members.
In order for myChoice HRD to be performed, the patient must have formalin-fixed paraffin-embedded tumor block or slides that contains at least 40 microns of tumor. The blocks or slides should contain at least 20% tumor by pathologic review.*
|Area of tumor (mm2)||# of 5 µm unstained slides|
*myChoice HRD is not currently available to patients who live in NY
- Mirza et al. N Engl J Med (2016). 375:2154-2164.
- Ledermann et al. Lancet Oncol. (2014). 15:852-61.
- Kristeleit et al. Presented at European Cancer Congress 2016 (Abstract 8560).
- Dougherty et al. (Oncotarget 2017 8(27):43653-43661).
- Lheureux et al. J Clin Oncol (2015). 33 (suppl;abstr 5566).
- Abkevich et al. Br J Cancer (2012) 107:1776-1782.
- Popova et al. Cancer Res (2012) 72(21):5454-62.
- Birkback et al. Cancer Discov (2012) 2(4):366-75.
- Yates et al. Annals of Oncology (2014) 25 (suppl_4): iv305-iv326.
- The Cancer Genome Atlas. Nature (2011) 474:609-615.
- Timms et al. Br Ca Res (2014) 16:475-483.
- Telli et al. Clin Cancer Res (2016). In Press.
- Mills et al. Presented at 2016 SGO Annual Meeting on Women’s Cancer (abstract 2).
- Norquist et al. Presented at 2016 SGO Annual Meeting on Women’s Cancer (abstract 1).