BRCA1-Hereditary Cancer of the Breast
- GTR Test IDHelpEach Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number. The format is GTR00000001.1, with a leading prefix 'GTR' followed by 8 digits, a period, then 1 or more digits representing the version. When a laboratory updates a registered test, a new version number is assigned.: GTR000021517.8
- Last updated: 2023-02-08
- Test version history
Clinical testHelpIn the U.S., clinical tests must be performed under CLIA certification. When a lab uses the same methods for a test in both clinical and research settings, the test appears as two separate GTR records. for Breast-ovarian cancer, familial, susceptibility to, 1
Offered by Molecular Genetics Laboratory
Overview
Test name
HelpThe name the laboratory assigns the test. Used as the default title of the page specific to the test.BRCA1-Hereditary Cancer of the Breast (BRCA1)
This is a clinical test intended for HelpPurposes or indications for the test. Lab-provided.: Diagnosis, Mutation Confirmation, Pre-symptomatic, Predictive, Prognostic, Recurrence, Risk Assessment
Click Indication tab for more information.
Please complete the requisition available on the website and ensure it is signed by the referring physician. Referrals only accepted through a cancer genetics clinic
Order URL HelpLink to the laboratory webpage with information about how to order this test. Please note that clicking on this link will open a new tab in your internet browser.: http://www.lhsc.on.ca/palm/molecular.html
Specimen source
Methodology
HelpThe assay's major method category (biochemical, cytogenetic or molecular genetics); method category (i.e. enzyme assay, chromosome breakage studies, targeted mutation analysis); methodology (i.e. the name of the method used) and instruments used when performing this test.- Molecular Genetics
- DDeletion/duplication analysis
- Multiplex Ligation-dependent Probe Amplification (MLPA)
- Applied Biosystems 3730 capillary sequencing instrument
- CSequence analysis of the entire coding region
- Next-Generation (NGS)/Massively parallel sequencing (MPS)
- Illumina MiSeq/NextSeq
- TTargeted variant analysis
- Bi-directional Sanger Sequence Analysis
- Agilent 2100 Bioanalyzer
- Agilent SureSelect
Establish or confirm diagnosis
Guidance for management
Avoidance of invasive testing
Predictive risk information for patient and/or family members
Clinical validity
HelpHow consistently and accurately the test detects or predicts the intermediate or final outcomes of interest. Lab-provided.A germline mutation in BRCA1 or BRCA2 predisposes to breast and ovarian cancer as well as other cancers. The risk of developing cancer that is associated with a germline BRCA1 or BRCA2 mutation, which has been derived from families with multiple affected individuals, families with few affected individuals, and from population-based studies, appears to be variable within families. Prognosis for breast and ovarian cancer depends on the stage at which the cancer is diagnosed; however, studies on survival have revealed conflicting results for individuals with germline BRCA1 or BRCA2 mutations when compared to controls.
- <i>BRCA1-</i> and <i>BRCA2</i>-Associated Hereditary Breast and Ovarian Cancer - PubMed ID: 20301425
- https://www.ncbi.nlm.nih.gov/books/NBK1247
Testing strategy
HelpThe lab's suggested sequence of ordering tests based on clinical scenarios. It may include information on: reflex testing including each test component, and scenarios which prompt additional components of testing; whether lab communicates interim results or automatically proceeds to further analyses; and if any components are performed in another laboratory.All coding exons and 20 bp of flanking non-coding sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >300x mean read depth coverage, with a minimum 100x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. Variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868), if necessary, are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. Variants detected in the 5’ UTR and 3’ UTR are not reported unless there is evidence suggesting pathogenicity. This assay has been validated at a level of sensitivity equivalent to the Sanger sequencing and standard copy number analysis (>99%; PMID: 27376475,28818680). 000 Please complete the requisition available on the website and ensure it is signed by the referring physician. Referrals only accepted through a cancer genetics clinic
Test services
HelpLaboratory's order or catalog code for the test (used in the order requisition form).- Clinical Testing/Confirmation of Mutations Identified Previously
- Confirmation of research findings
- Custom Deletion/Duplication Testing
- Custom Sequence Analysis
- Custom Prenatal Testing
- Custom mutation-specific/Carrier testing
- USPSTF, 2019Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force
- USPSTF, 2013Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation (See 2019 Update)
- Phillips et al., 2013Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
- Domchek et al., 2010Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality
- NCI PDQ, Cancer Genetics CounselingCancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version
- NCCN, 2022NCCN Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic version 2.2022
- NICE, 2019UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2019
- ACMG ACT, 2019American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019
IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.