BRCA1 and BRCA2 Mutations Explained

BRCA1 and BRCA2 are genes that everyone has. Their job is to make proteins that help repair damaged DNA. You carry two copies of each gene, one from each parent.

Some people inherit a harmful change in one of these genes. It is also called a mutation or a pathogenic variant. That change raises the risk of several cancers, most of all breast and ovarian cancer.

A harmful BRCA change raises cancer risk. It does not mean cancer is certain.

BRCA1 and BRCA2 help keep DNA healthy by fixing damage. Nearly everyone who inherits a harmful change in one gene still has a normal second copy from the other parent. One working copy is usually enough to protect cells.

But that normal copy can be lost or damaged during a person's life. When a cell loses its only working copy, it can no longer repair DNA well. It may then grow out of control and become cancer. That is why an inherited BRCA change raises risk without guaranteeing disease.

The National Cancer Institute reports that the risks are markedly higher for people with a harmful BRCA change. These figures are estimates, and published ranges vary with the study population:

• Breast cancer: More than 60 percent of women with a harmful BRCA change develop breast cancer in their lifetime. In the general population, about 13 percent of women do.
• Ovarian cancer: NCI estimates that about 39 to 58 percent of women with a harmful BRCA1 change develop ovarian cancer in their lifetime. For a harmful BRCA2 change, the estimate is about 13 to 29 percent. In the general population, about 1.1 percent of women do.
• Other cancers: Harmful BRCA changes also raise the risk of pancreatic cancer, prostate cancer, and male breast cancer.

People with a harmful BRCA change also tend to develop cancer at younger ages than others.

These are raised risks, not certainties. The numbers describe groups, not any one person.

BRCA changes are not only a concern for women. Men can inherit a harmful change. It raises their risk of male breast cancer and prostate cancer, and BRCA2 is especially linked to prostate cancer. Men can also pass the change to their children. So a father's BRCA status can matter for the whole family.

Harmful BRCA changes are rare — about 1 in 400 people in the general population. Some groups have a higher rate. About 2 percent of people of Ashkenazi Jewish descent carry one of three specific changes, called founder mutations. Other populations have their own founder mutations, including Norwegian, Icelandic, Hispanic, and West African groups. Different groups may carry different changes.

For people known to carry a harmful BRCA change, several options exist to manage risk. These are decisions to make with a care team, and this article does not recommend any path. In general, the options can include:

• Enhanced screening, such as starting breast screening younger and adding MRI to mammography
• Risk-reducing surgery, which removes at-risk tissue but has real trade-offs
• Risk-reducing medications in some situations

Each option has benefits and downsides, and no approach removes all risk.

BRCA status can also matter for people who already have cancer. Cancers with harmful BRCA changes may respond to certain DNA-damaging drugs. They may also respond to a class of medicines called PARP inhibitors. Sometimes a harmful BRCA change is first found when a tumor is tested. Such a change may be inherited, or it may have arisen in the tumor itself. A separate inherited-risk (germline) test can confirm whether it was passed down.

A harmful BRCA change raises risk. It is not a diagnosis and not a certainty. Testing uses a simple blood or saliva sample. Genetic counseling helps a person understand what a result would mean, for them and for their relatives, before and after any test. Knowing your family's cancer story and sharing it with your care team is the practical first step.