Inherited Genetic Mutations

Certain inherited genetic mutations have been linked to breast cancer. These include mutations in the following genes: BRCA1, BRCA2, p53, PTEN/ MMAC1 and CHEK2. Other genes are under study and may also play a role in breast cancer risk.

Although the known inherited mutations increase the risk of breast cancer, they are very rare in the general population. These mutations account for only five to 10 percent of all breast cancers diagnosed in the U.S. [4].

BRCA1 and BRCA2 genetic mutations  

BRCA1 and BRCA2 (standing for BReast CAncer gene 1 and 2) are the most well-known genes linked with breast cancer risk. BRCA1/2 mutations can be passed to you through your mother or your 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, but the prevalence varies by ethnic group.

BRCA1 and BRCA2 and female breast cancer

Women who carry a BRCA1 or BRCA2 genetic mutation have a much higher risk of breast cancer. Between 1 in 400 and 800 women in the U.S. are BRCA1 or BRCA2 carriers [5]. A woman's chance of getting breast cancer in her lifetime (assuming she lives until the age of 85) is about 12 percent if she does not have a BRCA1/2 mutation. Estimates of a woman's chance of getting breast cancer if she has a BRCA1 or BRCA2 mutation vary greatly. For BRCA1 carriers, the lifetime risk of breast cancer ranges from 60 to 90 percent. For BRCA2 carriers, estimates range from 30 to 85 percent [6-11]. This means that in a group of 100 women without a mutation, around 12 will develop breast cancer. While in a group of 100 women with either mutation, between 30 and 90 will develop breast cancer. 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. Also, the definition of lifetime risk varies among studies. Some studies measure risk assuming a woman lives to age 70; others use age 80 or age 85.

Together, the 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, even among BRCA1/2 carriers, genes do not equal destiny. Up to 40 percent of women with a BRCA1 mutation will never have breast cancer [6-11]. It is likely that a combination of factors determines who will get breast cancer.

BRCA1/2 mutations & risk factors

Researchers are studying whether certain factors that affect breast cancer risk in average women may also affect risk in BRCA1/2 carriers. Although most factors likely impact breast cancer risk in BRCA1/2 carriers just as in average women, some reproductive and lifestyle factors may not. This knowledge may help guide risk reduction strategies. For example, breastfeeding and physical activity as a teen appear to decrease the risk of breast cancer in both carriers and non-carriers of BRCA1/2 [12]. And, just as in women without a BRCA1/2 mutation, abortion, miscarriage, fertility drugs, IVF treatment and smoking do not seem to increase risk of breast cancer in BRCA1/2 carriers [13-17].

Some reproductive factors may affect breast cancer risk differently in BRCA1/2 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 [12,13,18,19]. And, a few studies have shown that having more children may increase risk in BRCA2 carriers [13,18,19]. 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 [12,18-23].

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 that is not related to the first one) for breast cancer survivors. The chance of a second primary cancer 10 years after diagnosis of the first cancer is about 30 percent for breast cancer survivors with a BRCA1/2 mutation compared to about 10 percent for survivors without BRCA1/2 mutations [24]. In young women with a BRCA1/2 mutation, the lifetime chance of a second primary tumor in the opposite breast may be as high as 60 percent [25].

BRCA1/2 mutations & risk of ovarian cancer

BRCA1/2 mutations also increase a woman's risk of ovarian cancer. For BRCA1/2 carriers, the risk of ovarian cancer by age 70 is about one to two percent [26]. A woman with a BRCA1 mutation has a 39 to 63 percent chance of ovarian cancer by age 70 [27]. And, for a woman with a BRCA2 mutation, this risk is 11 to 27 percent [27]. BRCA1/2 carriers can reduce their risk of both breast and ovarian cancer by having prophylactic oophorectomy (surgical removal of the ovaries) [28]. Find out more on prophylactic oophorectomy. The organization FORCE has on-line support for women affected by hereditary breast and ovarian cancer.

BRCA1/2 mutations & male breast cancer

Men can also carry BRCA1 or BRCA2 mutations and unfortunately may pass these mutations on to their children. BRCA2 mutations increase the risk of male breast cancer and may also raise the risk of prostate cancer [29-31]. BRCA1 carriers may also be at increased risk of male breast cancer, but this link is less clear. Although only five to 10 percent of female breast cancers are thought to be inherited, up to 40 percent of male breast cancers are due to genetic mutations [29]. The lifetime risk of breast cancer is 1 in 1000 for average men and about 60 to 70 in 1000 for men with a BRCA2 mutation [32,33].

Find out more on male breast cancer.

Find out more on genetic testing.

Find out more on risk-reducing options for women at higher risk. 
 

Updated 11/09/09

Family History/Genetic Risks

Family History of Breast, Ovarian or Prostate Cancer