Genetic testing for inherited breast cancer risk, often focusing on genes like BRCA1 and BRCA2, offers a powerful, personalized tool for health management. Understanding this test requires clarifying what the test is truly measuring. These tests reliably identify specific changes in a person’s DNA, but the results’ meaning for an individual’s lifetime risk depends on complex biological and statistical factors.
Understanding the Two Measures of Accuracy
The term “accuracy” in genetic testing is divided into two distinct concepts: analytical validity and clinical validity. Analytical validity addresses the technical precision of the laboratory process itself. This measure asks whether the test correctly identified the specific genetic variant—the change in the DNA sequence—if it was present in the sample. Modern sequencing technology is highly reliable for this purpose, ensuring the laboratory accurately detects the known genetic changes it is designed to find.
Clinical validity is a separate and more complex measure that connects the detected genetic change to the actual risk of developing breast cancer. This validity relies on large-scale population studies and medical evidence to determine how strongly a particular variant predicts the disease. A test may have perfect analytical validity by correctly identifying a gene change, but its clinical validity—the power to predict disease—is less than 100% because not everyone with a high-risk mutation will develop cancer.
Interpreting the Range of Test Outcomes
Genetic testing results provide three primary categories of outcomes, each with different implications for risk management.
Positive Result
A positive result indicates that a pathogenic or likely pathogenic variant was found in one of the tested genes, such as BRCA1 or BRCA2. This outcome confirms a significantly elevated lifetime risk of developing breast cancer, estimated to be between 45% and 85% for carriers of these specific mutations, compared to approximately 12% for the general population. Receiving a positive result usually leads to personalized risk-reduction strategies, including enhanced surveillance like annual MRI screenings and consideration of prophylactic surgeries.
Negative Result
A negative result signifies that no known pathogenic variant was found in the genes included in the test panel. For individuals with a known family mutation, a negative result means their risk returns to near-population levels. This result does not eliminate all breast cancer risk, however, since the majority of cancers are not hereditary.
Variant of Unknown Significance (VUS)
The third outcome is a Variant of Unknown Significance (VUS), which is often the most confusing for patients seeking clear answers about accuracy. A VUS is a change in the DNA sequence, but there is currently insufficient scientific data to classify it as either benign or pathogenic. VUS results are found in an estimated 10% to 15% of BRCA1/2 tests and are generally recommended to be disregarded in clinical decision-making. In such cases, a patient’s risk management plan continues to be based on their personal and family medical history, not the VUS result, until more evidence allows for reclassification.
Limits of Genetic Testing Scope
The predictive power of genetic testing is fundamentally limited by what the test is designed to measure. Current panels typically focus on a defined, limited set of genes, such as BRCA1, BRCA2, and PALB2, that confer a high individual risk. A negative result only confirms the absence of a harmful variant in those specific genes; it does not rule out the possibility of a mutation in other high-risk genes.
Genetic testing addresses only the hereditary component of risk, which accounts for an estimated 5% to 10% of all breast cancer cases. The vast majority of diagnoses are classified as sporadic, meaning they are acquired over a lifetime due to environmental, hormonal, and lifestyle factors. The inherited genetic test does not account for these non-hereditary risks, nor does it factor in established risk factors like obesity or dense breast tissue. Risk is also influenced by the combined effect of many common genetic variants, known as polygenic risk, which is distinct from the single, high-penetrance mutations tested in standard hereditary panels.