BRCA Gene Changes and Cancer Risk

BRCA1 and BRCA2 are genes that help repair damaged DNA in your cells. The names stand for "BReast CAncer gene 1 and 2." Everyone has two copies of each — one from each parent.

When someone inherits a harmful change in one of these genes, their cells are less able to repair DNA damage. This raises the risk of several cancers, most of all breast and ovarian cancer, and often at younger ages.

A harmful BRCA change raises risk a lot — but it is not a certainty, and there are real options to manage it.

Normally, BRCA1 and BRCA2 make proteins that fix damaged DNA. This repair helps keep cells healthy and stops them from growing out of control.

If you inherit one harmful copy, you usually still have a normal second copy that keeps cells protected. But if that normal copy is lost or damaged during life, the cell loses much of its repair ability — and that is when cancer can start.

BRCA changes raise risk because they weaken the body's DNA repair system.

Harmful BRCA changes raise the risk of several cancers. According to the National Cancer Institute:

• Breast cancer (women). More than 60 percent of women with a harmful BRCA change develop breast cancer in their lifetime, versus about 13 percent in the general population.
• Ovarian cancer. Risk is much higher than the roughly 1 percent seen in the general population, with the exact figure differing between BRCA1 and BRCA2.
• Breast cancer (men). Men with a harmful change, especially in BRCA2, have a higher risk than the very low general-population risk.
• Prostate cancer and pancreatic cancer risk are also raised, particularly with BRCA2.

Some other cancers may be linked as well, though those connections are less certain.

BRCA is not just a "breast cancer gene" — it affects several cancers and both men and women.

Harmful BRCA changes are uncommon in the general population — roughly 1 in 400 people. But they are more common in some groups.

For example, about 2 percent of people of Ashkenazi Jewish descent carry a harmful change, usually one of three specific ones. Other populations also have their own more common changes, called founder mutations.

Testing is generally focused on people more likely to carry a change. A doctor or genetic counselor may suggest it for someone with:

• A relative with a known harmful BRCA change
• Ashkenazi Jewish heritage
• A personal or family history of breast cancer at age 50 or younger
• A personal or family history of ovarian cancer, male breast cancer, pancreatic cancer, or high-risk or metastatic prostate cancer

Testing uses a blood or saliva sample. When possible, it often begins with a relative who has had cancer. Testing is not recommended for children, since there are no childhood risk-reduction steps and BRCA-related cancers are very unlikely in childhood.

• Positive. A harmful change was found, meaning higher risk of certain cancers. It does not mean cancer is certain — some carriers never develop cancer.
• Negative. Most meaningful when a specific family change is known and you did not inherit it. Otherwise it may not add much beyond your family history.
• Variant of uncertain significance. A change was found but its meaning is not yet clear; most are later found to be harmless. Until then, care is based on family history.

A result guides your plan — it does not decide your future.

People who carry a harmful BRCA change have several ways to manage risk, chosen with their care team:

• Enhanced screening. For women, this often means starting breast screening at younger ages and adding MRI to mammograms. No reliable ovarian cancer screening exists, so options for the ovaries focus on prevention. Men may be offered breast and prostate screening.
• Risk-reducing surgery. Some choose to have both breasts removed, or the ovaries and fallopian tubes removed, to lower risk. These surgeries are permanent and carry their own risks, and they cannot remove every at-risk cell.
• Risk-reducing medication. Certain medicines can lower breast cancer risk for some people, and some birth control options are linked to lower ovarian cancer risk. These have trade-offs too.

Each option has benefits and downsides. The right path depends on your health, values, and goals — which is why these are decisions to make with a knowledgeable care team.

Carrying a BRCA change gives you information and choices, not a fixed outcome.