Some inherited genetic mutations have been linked to breast cancer. These include mutations in the following genes:
- BRCA1
- BRCA2
- p53
- PTEN/ MMAC1
- CHEK2
- ATM
Other genes are under study and may also play a role in breast cancer.
Inherited mutations known to increase the risk of breast cancer are rare in the general population. These mutations account for only five to 10 percent of all breast cancers diagnosed in the United States. [4-6].
BRCA1 and BRCA2 genetic mutations
BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) are the most well-known genes linked to breast cancer risk. BRCA1/2 mutations can be passed to you through your mother’s or father’s side of the family and can affect the risk of both female and male cancers.
Like other genetic mutations, BRCA1/2 mutations are rare in the general population. In the U.S., between one in 400 and one in 800 people in the general population carry a BRCA1/2 mutation. However, prevalence varies by ethnic group. Among Ashkenazi Jewish men and women, about one in 40 carry a BRCA1/2 mutation [5].
Prevalence of BRCA1 and BRCA2 mutations by ethnic group (United States)
|
| |
BRCA1
|
|
BRCA2
|
Asian American
|
0.5%
|
African American
|
2.6%
|
African American
|
1.3-1.4%
|
Caucasian
|
2.1%
|
Caucasian (non-Ashkenazi Jewish)
|
2.2-2.9%
|
|
|
Hispanic
|
3.5%
|
|
|
Ashkenazi Jewish
|
8.3-10.2%
|
|
|
Adapted from National Cancer Institute materials [5].
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BRCA1 and BRCA2 and female breast cancer
Women who carry a BRCA1 or BRCA2 genetic mutation have an increased risk of breast cancer [7-14]. Estimates of this increased risk vary greatly. Women who carry a BRCA1 gene mutation have a 60 to 90 percent chance of developing breast cancer by age 70. For BRCA2 carriers, estimates range from 40 to 85 percent [7-14]. Women in the general population have about an eight percent chance of developing breast cancer by age 70 [6]. (Lifetime risk of breast cancer, defined as up to age 85, is about 12 percent [6].)
This means in a group of 100 women without a mutation, about eight will develop breast cancer by age 70 (about 12 by age 85). While in a group of 100 women with a BRCA1 or BRCA2 mutation, between 40 and 90 will develop breast cancer by age 70. Because these numbers represent average risk, the risk of breast cancer for any one woman with a BRCA1/2 mutation may fall outside this range.
Together, BRCA1 and BRCA2 genes are thought to explain a large portion of hereditary breast cancers [5]. However, most breast cancers are not hereditary or genetic. And, not all BRCA1/2 carriers will get breast cancer. Up to 40 percent of women with a BRCA1 mutation will never have breast cancer [7-14]. Thus, a combination of factors likely determines who will get breast cancer.
Learn more about risk-reducing options for women at higher risk.
Learn about genetic testing.
BRCA1/2 mutations and triple negative breast cancer
Women who carry a BRCA1 or BRCA2 mutation tend to have breast cancers that are triple negative [15-16]. Triple negative breast cancers are:
Learn about hormone (estrogen and progesterone) receptor status, HER2/neu status and other factors that affect prognosis and treatment.
Learn more about triple negative breast cancer.
Learn about molecular subtypes of breast cancer.
BRCA1/2 mutations & risk factors
Most risk factors for breast cancer likely impact breast cancer risk in BRCA1/2 carriers just as in non-carriers. This knowledge may help guide risk reduction strategies. For example, physical activity and breastfeeding appear to decrease the risk of breast cancer in both BRCA1/2 carriers and non-carriers [17-18]. And, for carriers and non-carriers alike, abortion, miscarriage, fertility drugs, IVF treatment and smoking do not seem to increase risk of breast cancer [19-23].
Certain reproductive and lifestyle factors may affect risk differently for BRCA1/2 carriers than non-carriers. Although having children and a younger age at first birth lower the risk of breast cancer in average women, some studies show no link between these factors and decreased risk among BRCA1/2 carriers [17,19,24-25]. And, a few studies have shown that having more children may increase risk in BRCA2 carriers [19,24-25]. While starting menstrual periods at an earlier age and current or recent use of birth control pills increase the risk of breast cancer in average women, it is unclear whether these factors affect risk in BRCA1/2 carriers [17,24-30].
BRCA1/2 mutations & risk of a second primary breast cancer
A BRCA1/2 mutation can increase the risk of a second primary breast cancer (a second breast tumor not related to the first one). These tumors usually occur in the contralateral (opposite) breast rather than in the same breast as the first cancer. For BRCA1/2 carriers, the chance of a contralateral breast cancer 10 years after diagnosis of the first cancer is about 13 to 30 percent compared to about five to 10 percent for breast cancer survivors without a BRCA1/2 mutation [31-35]. The lifetime chance of a second primary contralateral breast cancer is about 30 to 65 percent for BRCA1 carriers and about 50 to 60 percent for BRCA2 carriers [8,13,31-35].
BRCA1/2 mutations & risk of ovarian cancer
BRCA1/2 mutations also increase a woman's risk of ovarian cancer. For an average woman, the lifetime risk of ovarian cancer is about 1.5 percent [36]. However, lifetime risk of ovarian cancer for BRCA1 carriers is estimated at 35 to 70 percent [36]. And, for BRCA2 carriers, this risk is 10 to 30 percent [36].
BRCA1/2 carriers can reduce their risk of both breast and ovarian cancer by having prophylactic oophorectomy (surgical removal of the ovaries) [37]. Learn more about prophylactic oophorectomy.
BRCA1/2 mutations & male breast cancer
Men can also carry BRCA1/2 mutations and may pass these mutations on to their children.
BRCA2 mutations increase the risk of male breast cancer and may also increase the risk of prostate cancer [9,14,38]. BRCA1 carriers may also be at increased risk of male breast cancer, but this link is less clear [5]. While five to 10 percent of female breast cancers are considered to be due to gene mutations, up to 40 percent of male breast cancers may be related to BRCA2 mutations [39]. The lifetime risk of breast cancer is 1 in 1,000 for average men and about 65 in 1,000 for men with a BRCA2 mutation [35,40].
Learn more about male breast cancer.
Learn about genetic testing.
Support for BRCA1/2 carriers
Some support groups are tailored for people with BRCA1/2-related breast cancers. For example, the organization FORCE has on-line support for women affected by hereditary breast and ovarian cancer. Our Support section offers a list of resources to help find a local or on-line support group.
Updated 11/10/11
