Everyone possesses the BRCA1 and BRCA2 genes, which are classified as tumor suppressor genes. Their normal function involves producing proteins that help maintain the stability of a cell’s genetic material. When these genes acquire a harmful change, known as a mutation, their protective function is compromised. This failure leads to an increased risk of developing certain cancers across a person’s lifetime.
The Role of BRCA Genes in DNA Repair
The proteins created by the BRCA1 and BRCA2 genes act as “caretakers” responsible for maintaining the integrity of the human genome. Their job is to repair specific types of damage that occur to DNA, particularly double-strand breaks. These breaks are severe injuries that can lead to large-scale chromosomal rearrangements if not corrected.
The BRCA proteins coordinate a repair process called homologous recombination, which uses an undamaged copy of the DNA as a template to fix the break. When a person inherits a non-functional copy of BRCA1 or BRCA2, this repair pathway is impaired. The cell must then rely on less accurate repair mechanisms, which introduce errors and mutations into the DNA sequence.
Over time, the accumulation of these genetic mistakes disrupts other regulatory pathways within the cell. This genomic instability creates an environment where a cell is more likely to transform into a cancerous one. The presence of a BRCA mutation does not guarantee cancer, but it significantly increases the probability of uncontrolled growth.
Understanding Hereditary Cancer Risk
A mutation in BRCA1 or BRCA2 carries an elevated risk for several specific types of cancer, beyond breast and ovarian cancer. For women, the lifetime risk of developing breast cancer is estimated to be between 45% and 85%, compared to 12% in the general population. Ovarian cancer risk is also elevated, with lifetime probabilities ranging from 10% to 46% for carriers, depending on the specific gene involved.
The specific gene affected influences the pattern of risk. BRCA1 mutations are often associated with triple-negative breast cancer, while BRCA2 mutations carry a higher risk for male breast cancer, prostate cancer, and pancreatic cancer. The concept of penetrance describes the probability that a person with the mutation will develop cancer. This risk is not 100% and varies based on the specific gene, cancer type, and other genetic and environmental factors.
The inheritance pattern for BRCA mutations is autosomal dominant, meaning only one copy of the mutated gene needs to be passed down from either parent. A person who carries a BRCA mutation has a 50% chance of passing that genetic change to each child. This pattern makes a detailed family history a strong indicator for who might carry the mutation.
Deciding on Genetic Testing
The decision to pursue genetic testing for BRCA mutations begins with a thorough risk assessment. This process usually involves meeting with a genetic counselor who reviews a person’s medical and family history. Criteria suggesting a high likelihood of carrying a mutation include:
- A diagnosis of breast cancer before age 50.
- A history of ovarian or pancreatic cancer at any age.
- A known BRCA mutation in a close blood relative.
- A diagnosis of triple-negative breast cancer before age 60.
- Men diagnosed with breast cancer at any age.
- Individuals of Ashkenazi Jewish heritage, due to a higher prevalence of specific BRCA mutations.
The test itself is straightforward, typically requiring a blood or saliva sample that is analyzed in a laboratory.
Genetic counseling is an important step both before and after the test, helping individuals understand the potential results and implications for themselves and their relatives. A pre-test session ensures the person is prepared for the medical consequences of a positive result, which informs medical decisions. Post-test counseling helps interpret the results (positive, negative, or a variant of uncertain significance) and outlines the next steps for risk management.
Proactive Risk Management Strategies
For individuals who test positive for a BRCA mutation, proactive strategies are available to manage and reduce cancer risk. These strategies fall into two main categories: enhanced surveillance and preventive intervention. Enhanced surveillance involves using advanced and frequent screening methods to detect cancer at its earliest, most treatable stages.
For women, this often means beginning breast cancer screening around age 25, alternating between annual mammograms and breast magnetic resonance imaging (MRI). The MRI is more sensitive than a standard mammogram and is useful for screening the dense breast tissue often found in younger women. Clinical breast examinations are also recommended every six to twelve months.
Preventive intervention strategies involve medical or surgical action to lower risk. Risk-reducing bilateral mastectomy (surgical removal of both breasts) can reduce the risk of breast cancer by more than 90%. Another effective intervention is risk-reducing salpingo-oophorectomy (RRSO), the removal of the ovaries and fallopian tubes.
RRSO is the most effective way to prevent ovarian cancer, reducing the risk by over 80%. It also lowers breast cancer risk if performed before menopause. The optimal timing for RRSO is recommended between ages 35 and 40 for BRCA1 carriers and between 40 and 45 for BRCA2 carriers. Chemoprevention, using medications like tamoxifen or raloxifene, offers a non-surgical option that can reduce breast cancer risk.