The BRCA1 and BRCA2 genes, derived from “BReast CAncer gene,” normally act as tumor suppressors. These genes produce proteins that are primarily responsible for repairing damaged DNA, thereby maintaining the stability of the cell’s genetic material. When a person inherits a harmful change, or mutation, in one of these genes, the resulting protein may be non-functional. This leaves the individual with a significantly higher lifetime risk of developing certain cancers, most notably breast and ovarian cancers. Understanding the possibility of carrying one of these mutations through genetic testing allows for the implementation of risk-reducing strategies.
Determining the Need for Genetic Testing
The decision to pursue genetic testing for BRCA mutations is generally recommended for those who meet specific criteria that indicate a higher likelihood of carrying the mutation. Personal history of certain cancers is a strong indicator. This includes breast cancer diagnosed at age 50 or younger, triple-negative breast cancer at any age, or a diagnosis of ovarian, fallopian tube, or peritoneal cancer. A history of male breast cancer or metastatic prostate cancer also suggests the need for testing, as BRCA mutations increase the risk for these cancers.
Family history is another major factor. Testing is often recommended if multiple close relatives have been diagnosed with breast cancer, especially before age 50, or if a BRCA mutation is already identified in the family. Individuals with a blood relative who has had ovarian, pancreatic, or high-grade prostate cancer may also be candidates. Furthermore, specific ancestral backgrounds, such as being of Ashkenazi Jewish descent, are associated with a higher prevalence of certain BRCA mutations and warrant consideration.
Prior to testing, patients typically undergo genetic counseling. A genetic counselor assesses the individual’s risk based on their personal and family medical history. They explain the potential implications of the results, including the emotional and social impact. This session ensures the patient understands the benefits and limitations of the test and addresses concerns, such as legal protections against genetic discrimination afforded by the Genetic Information Nondiscrimination Act (GINA).
Steps Involved in Sample Collection and Analysis
Once the decision to proceed is made, the test is typically ordered by a genetic counselor, oncologist, or primary care physician. Collecting the DNA sample is straightforward and non-invasive in most cases. The most common methods involve either a blood draw from a vein in the arm or the collection of a saliva sample using a specialized kit.
The collected sample is sent to a specialized laboratory for analysis. Technicians use advanced sequencing technology to examine the BRCA1 and BRCA2 genes. This process involves reading the DNA sequence to identify any harmful changes or pathogenic variants. Laboratory analysis typically takes two to four weeks, with results delivered to the ordering healthcare provider.
Interpreting the Test Outcomes
Genetic testing for BRCA mutations yields one of three primary outcomes. A positive result indicates that a pathogenic or likely pathogenic variant—a known harmful mutation—was identified in either the BRCA1 or BRCA2 gene. This finding means the individual has an increased lifetime risk for developing certain cancers, but it does not predict if or when cancer will occur.
A negative result means that no known harmful BRCA mutation was found. If a specific mutation was already identified in the family, a negative result confirms the individual did not inherit that specific change (a true negative). For individuals without a known family mutation, a negative result means their risk is comparable to the general population.
The third possibility is a Variant of Uncertain Significance (VUS). This represents a change in the gene sequence that cannot currently be classified as clearly harmful or harmless. VUS results are common, especially with multi-gene panel tests, and generally do not impact current medical management decisions, which continue to be based on personal and family history. Most VUS findings are eventually reclassified as benign over time as more scientific data becomes available, but until then, they are treated as inconclusive.
Clinical Management Following a Positive Result
A positive BRCA result leads to enhanced cancer surveillance and risk reduction strategies. For women, enhanced surveillance includes regular breast magnetic resonance imaging (MRI) and mammograms starting at an earlier age, often MRI at 25 and mammography at 30. Clinical breast examinations are also recommended every six to twelve months.
For ovarian cancer risk, routine screening using transvaginal ultrasound and the CA-125 blood test has limited effectiveness for early detection. The most effective risk-reducing measure is surgical intervention: a prophylactic bilateral salpingo-oophorectomy. This procedure involves removing the ovaries and fallopian tubes, which significantly reduces ovarian cancer risk and decreases breast cancer risk by removing hormone-producing organs.
Another definitive risk-reduction option for breast cancer is a prophylactic mastectomy, which can reduce the risk by 90% or more. Chemoprevention, using medications like tamoxifen, can also be discussed as a non-surgical option. These management decisions are highly individualized, considering the patient’s age, specific BRCA mutation, and desire for future childbearing.