Genetic testing for breast cancer susceptibility identifies inherited mutations that increase a person’s lifetime risk of developing the disease. This is distinct from testing a tumor itself, as it analyzes germline DNA—the genetic information passed down from parents—to find variations that significantly disrupt normal cell function. The results potentially lead to medical decisions that dramatically alter cancer risk. Weighing the clinical utility of the information against the personal implications is the central question for anyone considering this diagnostic tool.
Eligibility Criteria for Testing
Genetic testing eligibility is based on established medical criteria, usually involving a detailed personal and family history of cancer. Current guidelines from organizations like the National Comprehensive Cancer Network (NCCN) target individuals whose results would directly impact their medical management. The presence of multiple close relatives on the same side of the family with breast, ovarian, pancreatic, or prostate cancer often meets the threshold for testing.
A diagnosis of breast cancer at a young age, typically 45 or younger, is a strong indicator for testing, even without a significant family history. Specific cancer types, such as triple-negative breast cancer diagnosed at age 60 or younger, or any male breast cancer diagnosis, also qualify a person for consideration. Individuals with Ashkenazi Jewish ancestry also warrant genetic counseling and potential testing due to a higher prevalence of certain founder mutations.
Understanding the Genes and Results
Genetic testing primarily focuses on high-penetrance genes, most notably BRCA1 and BRCA2, which are responsible for a large percentage of hereditary breast and ovarian cancers. These genes normally help repair damaged DNA, and an inherited pathogenic mutation severely impairs this repair function. Modern testing often uses multi-gene panels to simultaneously check for mutations in other genes, such as PALB2 and CHEK2, which are also associated with increased cancer risk.
A positive result means a pathogenic or likely pathogenic mutation has been identified, such as in BRCA1 or BRCA2. This can raise the lifetime risk of developing breast cancer to between 50% and 85%, compared to the general population’s risk of about 13%. A negative result indicates the individual does not carry the specific mutation tested.
A third outcome is a Variant of Uncertain Significance (VUS), which occurs when a change in the DNA is found but its clinical meaning is not yet known. These uncertain findings are not typically used to guide medical decisions, which instead remain based on the patient’s personal and family history. Laboratories continuously reclassify VUS results as scientific understanding improves. The larger the number of genes tested on a panel, the higher the chance of receiving a VUS result.
Proactive Management Based on Results
A positive result is not a diagnosis of cancer, but rather a warning that allows for the implementation of risk-reduction strategies. These strategies fall into three main categories: increased surveillance, chemoprevention, and risk-reducing surgery. The goal of this proactive management is to either detect cancer at its earliest, most treatable stage or to prevent its development altogether.
Increased surveillance involves starting screenings at a much younger age and using more sensitive imaging tools. For carriers of a BRCA mutation, guidelines recommend beginning annual breast magnetic resonance imaging (MRI) scans, often starting at age 25, followed by annual mammography starting at age 30, with the two screenings performed six months apart. This intensive schedule is designed to catch cancers associated with these mutations early.
Chemoprevention involves the use of certain medications to reduce the cancer risk. Drugs like Tamoxifen, a selective estrogen receptor modulator, can be prescribed to reduce the risk of developing hormone-receptor-positive breast cancer. Chemoprevention offers a non-surgical alternative for risk reduction, though its use must be weighed against potential side effects.
Risk-reducing surgery is the most effective preventive measure. A prophylactic bilateral mastectomy (the surgical removal of both breasts) can reduce the risk of breast cancer by 90% or more. Similarly, a risk-reducing salpingo-oophorectomy (the removal of the ovaries and fallopian tubes) is recommended for BRCA carriers, typically between the ages of 35 and 45 depending on the specific mutation. This procedure not only prevents ovarian cancer, for which there are no effective screening tools, but also reduces breast cancer risk by removing the primary source of estrogen.
Non-Medical Considerations
Receiving a result, whether positive or negative, can provoke intense emotional reactions. Genetic counseling is offered both before and after testing to help individuals process the complex information and cope with the psychological impact of the results.
The cost of genetic testing has become much more accessible, yet it remains a factor for some individuals. Out-of-pocket costs for a simple BRCA1/2 test can be as low as $250, but a comprehensive multi-gene panel without insurance coverage may cost between $1,500 and $5,000. Insurance coverage is typically granted if a person meets the established medical criteria, but this often requires pre-authorization and can involve an appeals process.
Concerns about genetic discrimination are a common barrier to testing, leading to fears that results could affect employment or insurance. The Genetic Information Nondiscrimination Act (GINA), enacted in 2008, offers federal protection against the misuse of genetic information in health insurance and employment decisions. GINA does not extend its protections to life insurance, disability insurance, or long-term care insurance.