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.
Hereditary breast and ovarian cancer syndrome (HBOC)
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|