The BRCA1 and BRCA2 genes produce proteins that function as tumor suppressors. These proteins repair damaged DNA within cells, maintaining genetic stability. When a person inherits a harmful change, or pathogenic variant, in one of these genes, the DNA repair mechanism is compromised. This failure in DNA repair significantly increases the lifetime risk of developing certain cancers. The primary diseases associated with these inherited mutations are hereditary breast and ovarian cancers, but they also elevate the risk for prostate and pancreatic cancers.
Determining If Testing Is Necessary
Genetic testing for BRCA mutations is not recommended for the general population but is strongly considered for individuals whose personal or family history suggests an elevated risk. A trained healthcare professional or genetic counselor assesses this risk by reviewing specific criteria. Family history indicators are paramount in this assessment, particularly having multiple close relatives diagnosed with breast, ovarian, prostate, or pancreatic cancer.
Factors for testing include a diagnosis of breast cancer at a young age. The presence of male breast cancer in the family at any age is also a strong indicator, as is a personal or family history of ovarian, fallopian tube, or peritoneal cancer. Furthermore, individuals who have Ashkenazi Jewish ancestry have a higher prevalence of specific BRCA founder mutations.
Genetic counseling plays an important role in the process. The counselor helps the individual understand the potential benefits and limitations of testing, ensuring the decision to proceed is fully informed. This consultation involves a detailed discussion of the personal and family medical history to determine the likelihood of carrying a mutation.
Steps in the Genetic Testing Process
The first logistical step involves the collection of a biological sample. This sample is most commonly obtained through a simple blood draw performed in a clinic or lab setting.
In some cases, a saliva sample or a cheek swab may be collected instead of blood. The sample is then sent to a specialized genetics laboratory where the DNA is extracted and prepared for sequencing.
Laboratory analysis involves using advanced technology to read the sequence of the BRCA1 and BRCA2 genes. The lab compares the patient’s gene sequence against known, healthy sequences to identify any pathogenic variants or changes. The entire process, from sample collection to the generation of a final laboratory report, typically involves a waiting period of a few weeks.
Interpreting the Test Results
The results of a BRCA genetic test generally fall into one of three distinct categories, each carrying different implications for cancer risk. A positive result indicates that a pathogenic or likely pathogenic mutation was identified in the BRCA1 or BRCA2 gene. This outcome confirms the presence of an inherited variant that significantly increases the lifetime risk of developing associated cancers. However, a positive result does not guarantee that cancer will develop, only that the predisposition is present.
A negative result signifies that no known harmful mutation was found in the BRCA genes tested. This outcome is often classified as a benign or likely benign variant, suggesting the individual’s risk is similar to that of the general population unless other strong family history factors remain. If a specific mutation was known to be in the family, a negative result means the individual did not inherit that particular variant, significantly reducing their hereditary risk.
The third possible outcome is a Variant of Uncertain Significance (VUS), which is a change in the gene sequence whose connection to disease risk is currently unknown. This means there is insufficient evidence to classify the variant as harmful or harmless. Medical management decisions are usually not based on a VUS result. Most of these variants are eventually reclassified as benign over time as more data becomes available. Results are typically delivered during a post-test counseling session with a genetic counselor, who can interpret the findings.
Medical Management Following a Positive Result
A positive BRCA result immediately shifts the focus from diagnosis to proactive risk management and prevention. This personalized pathway includes two main categories of intervention: increased cancer surveillance and risk-reducing procedures. Intensive surveillance protocols are designed to detect cancer at the earliest, most treatable stages. For women, this involves starting annual breast magnetic resonance imaging (MRI) screening, often alternating with mammograms, at a younger age than is standard for the general public.
Screening for ovarian cancer is less effective but may involve transvaginal ultrasounds and a blood test for the CA-125 protein, though these are not considered reliable early detection tools. Men with a BRCA mutation, particularly BRCA2, may be advised to undergo earlier and more frequent prostate cancer screening, including PSA testing. These surveillance measures aim for early detection rather than prevention.
Risk-reducing interventions offer the highest degree of cancer prevention and include prophylactic surgery. A risk-reducing bilateral mastectomy, which removes both breasts, can reduce the risk of breast cancer by over 90%. For ovarian cancer, the gold standard is a risk-reducing salpingo-oophorectomy, which involves removing the ovaries and fallopian tubes. Chemoprevention, which involves taking certain medications like tamoxifen, is another option to reduce the risk of hormone-sensitive cancers.