BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2) are genes that produce proteins that help repair damaged DNA. Everyone has two copies of each of these genes—one copy inherited from each parent. BRCA1 and BRCA2 are sometimes called tumor suppressor genes because when they have certain changes, called harmful (or pathogenic) variants (or mutations), cancer can develop.
People who inherit harmful variants in one of these genes have increased risks of several cancers—most notably breast and ovarian cancer, but also several additional types of cancer. People who have inherited a harmful variant in BRCA1 and BRCA2 also tend to develop cancer at younger ages than people who do not have such a variant.
A harmful variant in BRCA1 or BRCA2 can be inherited from either parent. Each child of a parent who carries any mutation in one of these genes has a 50% chance (or 1 in 2 chance) of inheriting the mutation. Inherited mutations—also called germline mutations or variants—are present from birth in all cells in the body.
Even if someone has inherited a harmful variant in BRCA1 or BRCA2 from one parent, they would have inherited a normal copy of that gene from the other parent (that’s because in most cases, embryos with a harmful variant from each parent cannot develop). But the normal copy can be lost or change in some cells in the body during that person’s lifetime. Such a change is called a somatic alteration. Cells that don’t have any functioning BRCA1 or BRCA2 proteins can grow out of control and become cancer.
How much does an inherited harmful variant in BRCA1 or BRCA2 increase a woman’s risk of breast and ovarian cancer?
A woman’s lifetime risk of developing breast and/or ovarian cancer is markedly increased if she inherits a harmful variant in BRCA1 or BRCA2, but the degree of increase varies depending on the mutation.
Breast cancer: About 13% of women in the general population will develop breast cancer sometime during their lives (1). By contrast, 55%–72% of women who inherit a harmful BRCA1 variant and 45%–69% of women who inherit a harmful BRCA2 variant will develop breast cancer by 70–80 years of age (2–4). The risk for any one woman depends on a number of factors, some of which have not been fully characterized.
Like women with breast cancer in general, those with harmful BRCA1 or BRCA2 variants also have an increased risk of developing cancer in the opposite (contralateral) breast in the years following a breast cancer diagnosis (2). The risk of contralateral breast cancer increases with the time since a first breast cancer, reaching 20%–30% at 10 years of follow-up and 40%–50% at 20 years, depending on the gene involved.
Ovarian cancer: About 1.2% of women in the general population will develop ovarian cancer sometime during their lives (1). By contrast, 39%–44% of women who inherit a harmful BRCA1 variant and 11%–17% of women who inherit a harmful BRCA2 variant will develop ovarian cancer by 70–80 years of age (2–4).