The BRCA1 and BRCA2 genes are tumor suppressors that produce proteins to repair damaged DNA, which helps maintain a cell’s genetic stability. Everyone inherits one copy of each gene from each parent. When a person inherits a harmful variant, or mutation, in one copy of either gene, the DNA repair process is compromised.
This impairment makes it more likely that cells will develop genetic alterations that can lead to cancerous growth. Having a BRCA mutation does not mean an individual will certainly develop cancer. Instead, it signifies a substantially increased risk for developing certain cancers over their lifetime. These inherited mutations account for a fraction of all cancers, as most cases are sporadic rather than hereditary.
Specific Cancers Associated with BRCA Mutations
Inherited mutations in the BRCA1 and BRCA2 genes are most famously linked to an increased risk of female breast cancer. BRCA1-associated breast cancers are frequently “triple-negative,” meaning they lack estrogen, progesterone, and HER2 protein receptors, which can make them more aggressive. BRCA2 mutations are more often associated with estrogen receptor-positive breast cancers.
The risk extends to men, who can develop breast cancer due to these mutations, with BRCA2 mutations conferring a higher lifetime risk than BRCA1. Ovarian cancer, which includes cancers of the fallopian tubes and primary peritoneum, is another cancer associated with these genetic variants. The reason these mutations preferentially affect breast and ovarian tissues is a defining feature of Hereditary Breast and Ovarian Cancer (HBOC) syndrome.
Beyond breast and ovarian cancers, BRCA mutations elevate the risk for other malignancies. Pancreatic cancer has a clear association, with both BRCA1 and BRCA2 mutations contributing to an increased lifetime risk. Prostate cancer risk is also increased, particularly for men with BRCA2 mutations, who may be diagnosed with more aggressive forms of the disease at a younger age. A connection to melanoma, a form of skin cancer, has also been observed.
Lifetime Cancer Risk Statistics
For women in the general population, the lifetime risk of developing breast cancer is about 13%. With a harmful BRCA1 mutation, this risk is between 55% and 72%, and with a BRCA2 mutation, the risk is between 45% and 69%.
The risk is also higher for ovarian cancer. While less than 2% of women in the general population will develop ovarian cancer, the lifetime risk for women with a BRCA1 mutation is estimated to be between 39% and 44%. For women carrying a BRCA2 mutation, that risk is between 11% and 17%.
For men with a BRCA2 mutation, the lifetime risk of developing breast cancer can be as high as 8%, compared to less than 0.1% in the general male population. Prostate cancer risk is also affected. About 10.6% of men in the general population will develop it by age 80, but for men with a BRCA1 mutation, the risk is about 7-26%, and for those with a BRCA2 mutation, it rises to 19-61%.
The lifetime risk of pancreatic cancer for an average person is about 1-2%. For individuals with a BRCA1 or BRCA2 mutation, this risk increases to approximately 5%.
Criteria for Genetic Testing
Healthcare providers use specific personal and family health history criteria to identify individuals who may benefit from BRCA genetic testing. A recommendation for testing may be made based on factors such as:
- A personal history of breast cancer diagnosed before age 50.
- A personal history of triple-negative breast cancer diagnosed at any age.
- A personal history of ovarian, fallopian tube, primary peritoneal, male breast, or metastatic prostate cancer.
- A close relative (parent, sibling, or child) with a known BRCA1 or BRCA2 mutation.
- A significant family history, such as multiple relatives on the same side of the family with breast cancer, or a combination of breast, ovarian, pancreatic, or prostate cancers.
- An Ashkenazi Jewish ancestry, which has a higher prevalence of specific founder mutations.
Genetic counseling is a standard part of the testing process. A genetic counselor helps an individual understand the test’s potential outcomes, interpret the results, and discuss the medical and emotional implications for themselves and their family.
Risk Management and Prevention Strategies
For individuals who test positive for a BRCA1 or BRCA2 mutation, there are established strategies to manage the increased cancer risk. These approaches are personalized with a healthcare team to either detect cancer at its earliest stage or to reduce the risk of it developing. The main strategies include enhanced surveillance, risk-reducing medications, and preventive surgery.
Enhanced surveillance involves more frequent and intensive cancer screenings. For breast cancer, this often means starting annual mammograms and breast MRIs as early as age 25. The combination of imaging can improve detection rates in dense breast tissue. For ovarian cancer, screening tools may be discussed, but their effectiveness is still debated, making risk-reducing surgery a more common recommendation.
Risk-reducing medications, or chemoprevention, offer another layer of protection. Drugs like tamoxifen and aromatase inhibitors block or lower estrogen levels and have been shown to reduce the risk of developing estrogen receptor-positive breast cancer. These are often considered for women who have not undergone preventive surgery.
Prophylactic, or risk-reducing, surgery provides the most effective means of lowering cancer risk. A risk-reducing mastectomy can lower the risk of breast cancer by 90% or more. A risk-reducing salpingo-oophorectomy (removal of ovaries and fallopian tubes) can decrease ovarian cancer risk by up to 96% and also reduces breast cancer risk in premenopausal women. These are major surgeries that require careful consideration with medical professionals.