The human body contains two tumor suppressor genes, BRCA1 and BRCA2, which produce proteins that help repair damaged DNA within cells and prevent uncontrolled cell growth. When a person inherits a harmful change, known as a pathogenic variant, in one of these genes, the DNA repair mechanism is compromised. This inherited variant significantly increases an individual’s lifetime risk of developing certain cancers, primarily breast and ovarian cancers, but also prostate and pancreatic cancers. The percentage of positive BRCA tests depends entirely on the specific population being tested.
Understanding BRCA and the Testing Process
BRCA testing identifies pathogenic variants within the BRCA1 and BRCA2 genes. A positive result confirms the presence of a pathogenic variant, indicating a significantly elevated inherited cancer risk. The test is a straightforward procedure, usually requiring only a blood or saliva sample for laboratory analysis.
Genetic counseling is required before testing. A counselor reviews the individual’s personal and family medical history to determine the likelihood of a pathogenic variant. This consultation also provides education on the potential results, the medical implications of a positive finding, and the psychological impact testing may have.
Results are classified as positive (pathogenic variant found), negative (no pathogenic variant found), or a variant of uncertain significance (VUS). A VUS indicates a change in the DNA sequence not yet definitively linked to an increased cancer risk. A VUS is not considered a positive result for clinical risk management.
Prevalence of Positive Results in Tested Populations
The percentage of positive BRCA tests varies dramatically between the general population and those who undergo clinical testing. In the general U.S. population, the prevalence of a pathogenic BRCA1 or BRCA2 variant is very low, estimated at approximately 0.2% to 0.3%, or about one in 400 people.
In contrast, the positive rate among individuals who meet clinical criteria is substantially higher. In cohorts with a personal or strong family history of related cancers, the positivity rate ranges from 4% to 10% of all tests performed. For the most highly selected, high-risk groups, such as those with a strong cancer history and specific ancestry, the rate can exceed 30%. This difference highlights that clinical testing is a targeted process designed to maximize the detection of at-risk individuals.
A significant number of individuals receive a Variant of Uncertain Significance (VUS) result. These VUS results occur because modern testing technology can detect many rare genetic changes. VUS results are typically found in 10% to 15% of BRCA tests and are treated similarly to a negative result until scientific evidence allows for reclassification.
Factors That Influence the Positive Rate
Strict guidelines govern who qualifies for testing, focusing on clinical and demographic factors that elevate the pre-test probability of carrying a pathogenic variant. A strong family history is one of the most predictive factors, especially when multiple close relatives have been diagnosed with breast, ovarian, prostate, or pancreatic cancer.
The age at which cancer is diagnosed also influences the positive result rate. A diagnosis of breast cancer before age 50 is a common criterion for testing, as inherited variants often manifest earlier. Individuals diagnosed with specific tumor subtypes, such as triple-negative breast cancer, have a higher chance of carrying a BRCA1 mutation, regardless of family history, because this subtype is frequently associated with the genetic pathway disrupted by the BRCA1 variant.
Certain demographic factors, particularly ancestry, also increase the positive test rate. For example, individuals of Ashkenazi Jewish descent have a much higher prevalence of three specific “founder mutations” in the BRCA1 and BRCA2 genes. About 2% of this population carries one of these three variants, which is roughly ten times the general population rate.
Management Strategies Following a Positive Result
A positive BRCA test result initiates a shift toward proactive risk management, starting with heightened surveillance. This involves more frequent and intensive cancer screening than the general population receives. For breast cancer risk, this typically means alternating annual mammograms and breast magnetic resonance imaging (MRI) scans beginning at a younger age.
Chemoprevention involves taking certain medications to reduce cancer risk. Selective estrogen receptor modulators, such as tamoxifen, have been shown to lower the incidence of breast cancer in high-risk women by blocking the effects of estrogen on breast tissue.
Prophylactic surgery is the most effective strategy for risk reduction. A risk-reducing bilateral mastectomy can lower the risk of breast cancer by over 90%. For ovarian cancer, the removal of the ovaries and fallopian tubes, known as a risk-reducing salpingo-oophorectomy, substantially reduces both ovarian cancer risk and, if performed before menopause, breast cancer risk.