This test analyzes the BRCA1 and BRCA2 genes, which are associated with hereditary breast and ovarian cancer syndrome (HBOC).
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
HBOC can also be ordered as part of a broader panel to test for different types of hereditary cancer, including breast, ovarian, endometrial, and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
The average woman’s lifetime risk of developing breast cancer is 12%; her risk for developing ovarian cancer is 1.3%. Most cases of these cancers are sporadic and are not due to hereditary factors, but approximately 5%-10% of breast and ovarian cancer cases are hereditary and due to an identifiable pathogenic variant in a disease-causing gene. HBOC accounts for the majority of hereditary breast and ovarian cancer cases in individuals with a strong family history or an early-onset diagnosis.
Individuals who have inherited a pathogenic variant have a dramatically higher risk of developing cancer, and many of these cancers can be difficult to detect and treat. It is extremely helpful to identify these high-risk individuals so that additional screening, surveillance, and interventions can be started. These efforts can result in risk-reduction and early diagnosis, which increases the chances of successful treatment and survival.
Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person. However, not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.
|Gene||Female breast cancer||Male breast cancer||Ovarian cancer*||Other associated cancers|
|BRCA1||Up to 87%||1%-2%||Up to 54%||Pancreatic|
|BRCA2||Up to 84%||Up to 8.9%||Up to 27%||Prostate, pancreatic, melanoma|
*Ovarian cancer risk includes fallopian tube and primary peritoneal cancers.
Pathogenic mutations in BRCA1 or BRCA2 account for the majority of hereditary breast and ovarian cancer cases in individuals with a strong family history or an early-onset diagnosis.
HBOC is inherited in an autosomal dominant pattern. The gene BRCA2 is also associated with autosomal recessive Fanconi anemia.
HBOC syndrome testing should be considered in individuals with a personal and/or family history of features, including:
Genetic testing criteria have also been established by the National Comprehensive Cancer Network (National Comprehensive Cancer Network. Genetic/Familial High Risk Assessment: Breast and Ovarian. Version 1.2015).
There are also some common general features suggestive of a hereditary cancer syndrome family. These include:
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.