In the last decade, genetic testing for cancer has become increasingly common. As more specific genetic variants are identified through testing, they need to be classified as to how they can affect a person's health. The BRCA Exchange is a free online resource that aims to improve interpretation of genetic testing for breast and ovarian cancer by organizing and providing information about BRCA1 and BRCA2 gene variants. The information is accessible to anyone via the BRCA Exchange website or the smartphone app.
Certain variations in BRCA1/BRCA2 genes can increase a person's risk for developing breast and ovarian cancer as well as other cancers, while other variants do not. Unfortunately, the clinical significance of nearly 40% of BRCA1/BRCA2 variants is still unknown. Creators of the BRCA Exchange hope to increase our knowledge of such variants by collecting existing BRCA1/BRCA2 data from clinicians and researchers worldwide and employing a panel of experts to interpret their clinical significance.
About 3% of breast cancers and 10% of ovarian cancers are due to a disease-causing variant in the BRCA1 or BRCA2 gene. For women with these variants, their lifetime risk of developing breast cancer can be as high as 72%, compared to a lifetime risk of about 12% for all women in the general population. Depending on which disease-causing variant(s) a woman has, her lifetime risk of developing ovarian cancer ranges from 17% to 44%, compared to a lifetime risk of about 1% for all women in the general population.
For men with a disease-causing BRCA1/BRCA2 variant, there is an increased risk of breast cancer and prostate cancer. Men and women with disease-causing BRCA variants are also at increased risk of pancreatic cancer.
While BRCA testing is not recommended for the general population, an individual with a personal or family history that suggests the possibility of the presence of a disease-causing BRCA1/BRCA2 variant may choose to undergo testing. The BRCA Exchange has the potential to impact the lives of many people—especially those with a BRCA1/BRCA2 variant of uncertain clinical significance as scientists are able to classify and share information on these variants. The resource allows healthcare practitioners to review the latest expert classifications of BRCA1/BRCA2 variants, so they can advise their patients on questions about cancer prevention, screening, and interventions.
In 2014, the Global Alliance for Genomics and Health (GA4GH) met to discuss the urgent need to expand gene-variant identification and clinical interpretation. Out of this meeting, the five-year BRCA Challenge was created to enhance the collection and sharing of BRCA1/BRCA2 variant data. This led to the recent launch of the BRCA Exchange repository. The BRCA Exchange aims to improve and promote the sharing of BRCA1/BRCA2 variant data, funded in part by the National Institutes of Health's National Cancer Institute and through the Cancer Moonshot initiative. A paper detailing the development of the BRCA Exchange was published on December 26, 2018 in the journal PLOS Genetics.
As of January 2019, the BRCA Exchange has cataloged nearly 21,700 BRCA1/BRCA2 variants from research and healthcare databases from 32 countries around the world. This included the Breast Cancer Information Core, ClinVar, and the Leiden Open Variation Database, as well as public population databases and information submitted by clinicians, laboratories, and researchers.
The BRCA Exchange employs an international expert panel called the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) to classify these BRCA1/BRCA2 variants using information from its global database. Variants are classified as "Benign/little clinical significance," "Likely benign," "Not yet reviewed," "Uncertain significance," "Likely Pathogenic" or "Pathogenic." Of the 7,256 variants ENIGMA has already classified, it identified about 4,829 variants as known causes of increased risk of breast or ovarian cancer (pathogenic).
Creators of the BRCA Exchange recognize that sharing their repository and data analyses with the public could lead to misinterpretation of genetic testing results. To reduce the risk of this, they emphasize that a patient's genetic testing results should always be interpreted with the help of a genetic counselor and/or other healthcare professionals.
To further ensure the accurate and safe use of their data, the BRCA Exchange plans to develop tools that would make their data more meaningful and useful to patients and patient advocates. They are also preparing materials specifically for genetic counselors, healthcare providers, and patient advocates.
People who use direct-to-consumer (DTC) genetic testing services may be tested for only a few, specific BRCA variants and receive their results directly. These individuals are encouraged to share their report with their healthcare practitioner and talk about their results. Their results will likely need to be confirmed by a clinical laboratory. BRCA Exchange uses select public databases (such as ClinVar) as sources of information on all known BRCA variants. Consumer genetic test results are not likely to be automatically included in this resource.
In addition to providing a resource for BRCA1/BRCA2 gene variant information, the BRCA Exchange shows how a global effort involving hundreds of organizations can come together to create a comprehensive, shared database—an infrastructure model that could be used to create similar databases for other diseases with strong genetic components.