Why BRCA Testing?

Germline BRCA1/2 Status Can Help You Determine Which Patients are Eligible for Treatment with PARP Inhibitor Therapy

Mutations in BRCA1 or BRCA2 cause Hereditary Breast and Ovarian Syndrome (HBOC). Now mutations in the BRCA1 and BRCA2 genes provide an indication for treatment with the PARP inhibitors Lynparza® (olaparib), Talzenna® (talazoparib) and Rubraca® (rucaparib).

Normally, the proteins produced by the BRCA1 and BRCA2 genes prevent cells from developing into cancer by aiding in the repair of mutations in other genes through a process known as double-stranded DNA repair. When one of these genes becomes ineffective due to a deleterious mutation, the cell can no longer perform double-stranded repair DNA and are homologous recombination deficient. HR deficiency can increase the risk for cancer, but is also a biomarker for certain targeted therapies to treat cancer when it develops

Cancer cells with a germline BRCA1/2 mutation are more susceptible to treatments that directly or indirectly damage DNA such as PARP inhibitor therapy or DNA damaging chemotherapy. Identifying your patients with a BRCA1/2 mutation makes it possible to utilize targeted therapy to more precisely identify and attack cancer cells. Testing for BRCA1/2 allows therapy to be personalized based on the biology of a patient. 1-3

BRCA Testing for Breast CancerBRCA Testing for Ovarian CancerBRCA Testing for Pancreatic Cancer

Sources:
  1. Robson et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med (2018). 377:523-533.
  2. Litton et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA mutation. N Engl J Med 2018;379:753-63.
  3. Moore et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med (2018). DOI: 10.1056/NEJMoa1810858.

Intended Use
PMA Intended Use Statement for BRACAnalysis CDx

BRACAnalysis CDx® is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein-coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR.

Results of the test are used as an aid in identifying patients who are or may become eligible for treatment with the targeted therapies listed in Table 1 in accordance with the approved therapeutic product labeling.

Table 1: Companion diagnostic indications

Tumor TypeBiomarkerTherapy
Breast CancerDeleterious or suspected deleterious mutations in BRCA1 and BRCA2 genesLynparza® (olaparib)
Talzenna® (talazoparib)
Ovarian CancerDeleterious or suspected deleterious mutations in BRCA1 and BRCA2 genesLynparza® (olaparib)-
treatment/maintenance
Rubraca® (rucaparib)
Pancreatic CancerDeleterious or suspected deleterious mutations in BRCA1 and BRCA2 genesLynparza® (olaparib)
Prostate CancerDeleterious or suspected deleterious mutations in BRCA1 and BRCA2 genesLynparza® (olaparib)

Detection of deleterious or suspected deleterious germline BRCA1 and BRCA2 mutations by the BRACAnalysis CDx test in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) or Rubraca® (rucaparib) maintenance therapy.

This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108

Limitation: In Ovarian Cancer, ~70% of tumor BRCA1 or BRCA2 mutation positive patients are estimated to have a germline mutation while ~30% of patients are estimated to have a somatic mutation. The BRACAnalysis CDx test detects germline mutations only, not somatic mutations from a patient’s blood sample. A negative result using the BRACAnalysis CDx blood test in ovarian cancer patients does not rule out the possibility of a somatic BRCA1 or BRCA2 mutation in tumor tissue from these patients.

Limitation: In Prostate Cancer, ~50% of tumor BRCA1 or BRCA2 mutation positive patients are estimated to have a germline mutation while ~50% of patients are estimated to have a somatic mutation. The BRACAnalysis CDx test detects germline mutations only, not somatic mutations from patient’s blood sample. A negative result using the BRACAnalysis CDx blood test in prostate cancer patients does not rule out the possibility of a somatic BRCA1 or BRCA2 mutation in tumor tissue from these patients.