What Is BRCA1? About the BRCA1 Mutation and More

Learn how the BRCA1 gene functions and how hereditary BRCA1 mutations impact breast cancer risk

Most people who develop breast cancer have no family history of the disease. The majority of breast cancers are sporadic, caused randomly by many factors including aging, the environment, and lifestyle. Family history, however, is a strong risk factor for breast cancer, with five to 10 percent of all breast cancers caused by inherited genetic changes.

Here, we explore the role of the well-known BRCA1 gene and how hereditary BRCA1 gene mutations increase breast cancer susceptibility.

What is the BRCA1 gene?

BRCA1 (BReast CAncer gene 1) is a gene that, when mutated, is associated with an increased risk of several cancers including breast cancer, and, particularly, triple-negative breast cancer (TNBC).

In 1994, BCRF investigator Dr. Mary-Claire King and her team at the University of California, Berkeley made the landmark discovery of the BRCA1 gene—the first gene associated with hereditary breast cancer. This discovery helped explain why some women who carry mutations in BRCA1 see a markedly increased risk of developing breast cancer. Since then, scientists have gained a deep understanding of the BRCA1 gene and its normal biological function, leveraging this knowledge to develop effective targeted treatments for BRCA1-driven cancers.

How does the BRCA1 gene function?

The BRCA1 gene codes for the breast cancer type 1 susceptibility protein (BRCA1 protein, also called simply BRCA1). BRCA1 is part of a group of proteins that repair DNA when both strands of its double helix are broken or when the strands are mismatched. As cells continually grow and divide, they depend on the integrity of each cell’s DNA and repairing any small errors that may occur during this process is essential for cells to function normally.

If the DNA cannot be repaired, the BRCA1 protein can also trigger cellular responses to DNA damage that block cell division and induce cell death. In this way, BRCA1 is a tumor suppressor. If the BRCA1 gene itself is mutated and does not function normally, damaged DNA is not repaired correctly, leading to an accumulation of genetic mutations and subsequent increased risk of developing breast cancer.

What is the BRCA1 gene mutation?

Like all genes, the BRCA1 gene is a sequence of DNA nucleotides within a larger package of DNA called a chromosome. The BRCA1 gene provides the blueprint for cells to make the BRCA1 protein. Everyone has two copies of BRCA1 within their chromosomes, one from each parent. Changes in DNA called mutations can be inherited from either parent in either copy of the BRCA1 gene and passed on to both sons and daughters. An inherited mutation is called a germline mutation.

Researchers have identified thousands of different mutations in BRCA1. Some of these BRCA1 gene mutations are harmful (pathogenic), some have no observed impact on health (benign), and some have uncertain significance (variants of uncertain significance, or VUS). Pathogenic BRCA1 mutations typically occur in just one copy of the gene.

Inherited breast cancer risk is most commonly associated with BRCA1 and BRCA2 genes although there are several other established breast cancer susceptibility genes. Certain pathogenic variants of BRCA1 or other breast cancer susceptibility genes can lead to hereditary breast-ovarian cancer syndromes (HBOC). HBOC accounts for 90 percent of all hereditary breast cancers. Since BRCA1 mutations can be passed to both sexes equally, families with HBOC have higher than normal rates of not only breast and ovarian cancers, but prostate, and pancreatic cancers as well. Because the term HBOC is misleading in that it implies that it affects women more than men, it is more recently also known as King syndrome, referencing Mary-Claire King.

How does a BRCA1 mutation impact breast cancer risk?

In the U.S. general population, about 12 percent of women will develop breast cancer in their lifetime. By contrast, 55 to 72 percent of women with a pathogenic BRCA1 mutation will develop breast cancer in their lifetime. Cancers caused by a BRCA1 mutation are also more likely to occur in younger women and are more likely to be TNBC, a more aggressive and difficult-to-treat subtype because it lacks specific treatment targets. Black women are more likely to be diagnosed with breast cancer at a younger age and with TNBC compared to white women, but the rates of inherited genetic mutations among both groups are similar.

Women who are breast cancer survivors and have an inherited BRCA1 mutation have an increased risk of developing breast cancer in the opposite breast that is almost three times greater than the general population.

In men, about 0.2 to 1.2 percent of those with a harmful BRCA1 mutation will develop breast cancer by age 70 compared to 0.1 percent of the general population. Male breast cancer survivors with a pathogenic BRCA1 mutation also have about 30 to 40 percent increased risk of developing breast cancer in the other breast within 20 years compared to about eight percent of survivors in the general population.

BRCA1 mutations across races and ethnicities

In the general population, high-risk mutations of BRCA1 or BRCA2—a related breast cancer susceptibility gene—are found in about 0.2 to 0.3 percent of people, but the prevalence is higher among certain populations. In fact, hereditary BRCA1 and BRCA2 mutations differ among geographic and ethnic populations and occur with high frequency in some groups.

Harmful mutations arose in the ancestors of relatively isolated populations and were passed on within the population over generations. These specific pathogenic BRCA1 and BRCA2 variants are called “founder” mutations. For example, among people with Ashkenazi Jewish ancestry, there is a high prevalence of three BRCA1 founder mutations in about two percent of the population. Other populations including Latin American, Norwegian, Dutch, Icelandic, West African, African American, Sephardi Jewish, and Bahamian also have unique BRCA1 founder mutations that lead to increased breast cancer risk.

BRCA1 vs. BRCA2

BRCA1 and BRCA2 are two distinct genes, but they are related in that both are involved in repairing damaged DNA and playing critical roles in maintaining genomic stability, which is essential for preventing cancer. They are both tumor suppressor genes, meaning their normal function helps to prevent cells from becoming cancerous.

BRCA1 and BRCA2 work together in the homologous recombination repair pathway, which is a precise method of repairing double-strand breaks in DNA. BRCA1 helps initiate the repair process, while BRCA2 helps in the repair itself by stabilizing the enzyme that actually performs the repair. Both genes are essential for the accurate repair of damaged DNA, and when either is mutated, the repair mechanism is compromised—increasing breast cancer risk.

BRCA1 and BRCA2 differ in the type of breast cancer they promote: BRCA1-associated breast cancers are typically TNBC, whereas BRCA2-associated breast cancers are more likely to be estrogen receptor (ER)–positive. Additionally, in women, the lifetime risk of ovarian cancer is higher for BRCA1, about 40 to 45 percent, compared to 10 to 20 percent for BRCA2. Men with a BRCA1 mutation have a 1 percent lifetime risk of breast cancer compared to a 6 percent lifetime risk for men with a BRCA2 mutation.

What to know about genetic testing for BRCA1

Genetic testing for hereditary BRCA1 and other breast cancer susceptibility gene mutations may be recommended based on your personal and family history of cancer, ancestry, and whether you have a family member with a genetic mutation. Because these mutations are inherited, they are present in the DNA of every cell in the body, including blood and saliva cells, which are easily collected.

Genetic counseling before testing is recommended to understand if you or your family members will likely benefit from it. If you have a family history of breast cancer, a genetic counselor may recommend using a multigene panel test that assesses mutations in several breast cancer susceptibility genes. For those with Ashkenazi or Eastern European Jewish ancestry, a genetic counselor may recommend testing for the three BRCA1 founder mutations commonly seen in that population. If a pathogenic BRCA1 mutation is found, parents, children, and siblings have a 50 percent chance of having the same mutation and may also consider genetic testing.

If a pathogenic BRCA1 mutation is found in a person who does not have cancer, genetic counselors and clinicians can advise on the next steps to take to prevent breast cancer or find and treat it as early as possible. Because the risk of breast and ovarian cancer is significant, many BRCA1 mutation carriers choose to have risk-reducing surgery: removing both breasts (bilateral mastectomy) and/or both ovaries (bilateral prophylactic oophorectomy). Bilateral mastectomy reduces the risk of breast cancer by 95 percent in pathogenic BRCA1 mutation carriers.

Suppose genetic testing does not reveal a BRCA1 mutation previously found in another family member. In that case, this indicates that the mutation was not inherited, and the risk of developing breast cancer is no higher than in the general population.

If a pathogenic BRCA1 mutation is found in a person who currently has breast cancer, knowing this information can help guide treatment decisions. If a BRCA1 mutation is not found, it is likely a hereditary BRCA1 mutation did not cause the cancer, and genetic testing of family members is not likely to be helpful.

Researchers have identified BRCA1 variants of uncertain significance (VUS), meaning that it is unknown whether that particular mutation causes cancer. In this case, further testing may be available.

BCRF’s BRCA1 and TNBC Research

BCRF investigators are working tirelessly to improve care for BRCA1 and BRCA2 mutation carriers and expand treatments for TNBC, which can be BRCA1-driven. This includes improving genetic testing for families carrying breast cancer susceptibility gene mutations and populations at higher risk of having BRCA1 and BRCA2 founder mutations. They are working to better understand the risk conferred by the thousands of known BRCA1 and BRCA2 gene mutations and to turn this improved risk assessment into actionable care decisions. Researchers are also optimizing screening for BRCA1 and BRCA2 mutation carriers and working to introduce preventative options beyond risk-reducing surgeries, including vaccines.

The majority of breast cancers arising from pathogenic BRCA1 mutations—between 66 and 100—are TNBC, an aggressive subtype that currently lacks targeted treatments. BCRF researchers have leveraged the discovery that TNBCs can differ from patient to patient and respond differently to therapies in order to develop new drugs and drug combinations that better target an individual’s disease.

PARP inhibitors target cells’ “backup” DNA repair pathway when BRCA1- and BRCA2-mediated DNA repair is not functional because of a gene mutation. PARP inhibitors hinder cellular DNA repair, meaning those cells no longer have a backup plan and cannot survive. Investigators are conducting clinical trials testing PARP inhibitors alone or in combination with other therapies for treating BRCA1- and BRCA2-mutated breast cancers.

Antibody-drug conjugates (ADCs) can deliver chemotherapy directly to cancer cells while sparing healthy cells. This technology has opened up new options for treating TNBC and some HER2-low breast cancers that were previously classified as TNBC. Trastuzumab deruxtecan (Enhertu®) received FDA approval to treat HER2-positive advanced breast cancer with low levels of HER2 (in 2022) and ultralow levels of HER2 (as of 2025). The ADC sacituzumab govitecan (Trodelvy®) was FDA approved for metastatic TNBC in 2020 based on studies from BCRF investigators and others. Research is ongoing to optimize ADC treatment for breast cancer.

Researchers are also leveraging the immune system to eradicate cancer more effectively, particularly since immunotherapy has had some success in the clinic treating TNBC. For example, ongoing studies are utilizing checkpoint inhibitors, a form of immune therapy. They work by targeting and blocking certain proteins that act as “brakes” on the immune system, allowing the immune system to recognize and attack cancer cells more effectively.

PARP inhibitors, antibody-drug conjugates, and immunotherapies are just a few examples of how BCRF investigators are seeking to improve treatment options and breast cancer management for BRCA1 mutation carriers. Leading research into BRCA1 pathogenic mutations and TNBC from so many angles, our investigators can make significant strides toward optimal care for those who are at high risk of developing breast cancer.