A number of inherited mutations have been linked to breast cancer, including mutations in the following genes: BRCA1, BRCA2, p53 and PTEN/ MMAC1. Other genes are currently being studied for their role in breast cancer risk.
Although the known inherited mutations greatly increase the risk of developing breast cancer, they are very rare in the general population and account for only 5 to 10 percent of all breast cancers diagnosed in the U.S. [2].
BRCA1/BRCA2 and Breast Cancer
Of the genes linked with breast cancer risk, BRCA1 and BRCA2 (standing for BReast CAncer gene 1 and 2) are the most well-known. It is estimated that about 250,000 women in the United States carry a BRCA1 or BRCA2 mutation, and these women have a much higher risk of breast cancer.
A woman's chance of developing breast cancer in her lifetime (assuming she lives until the age of 85) is about 12 percent if she does not have a BRCA1 or BRCA2 mutation. Estimates of a woman's chance of developing breast cancer if she has a BRCA1 or BRCA2 mutation vary greatly. For women with a BRCA1 mutation, the chance of developing breast cancer within her lifetime ranges from 60 to 90 percent. And for women with a BRCA2 mutation, estimates range from 30 to 85 percent [10-14]. This means that in a group of 100 women without a mutation, around 12 will develop breast cancer in their lifetimes. While in a similarly sized group of women with either mutation, somewhere between 30 and 85 will develop breast cancer. Because these numbers represent average risk, the risk of breast cancer for an individual woman with a BRCA1 or BRCA2 mutation may fall outside this range. Also the definition of lifetime varies among studies. Some studies measure risk assuming a woman lives to 70, others use age 80 or age 85.
Together, mutations in the BRCA1 and BRCA2 genes are thought to explain a large portion of hereditary breast cancer cases [2]. However, most breast cancers are not hereditary or genetic. And, even in the case of BRCA mutations, genes do not seem to equal destiny. Up to 40 percent of women with a BRCA1 mutation will never have breast cancer. It is likely that a combination of factors determines who will develop breast cancer. In fact, recent research suggests that certain lifestyle factors, including breastfeeding and being physically active during adolescence, may help reduce breast cancer risk in women with BRCA mutations [13,16].
BRCA Mutations & Risk of a Second Primary Breast Cancer
Among women who have already had breast cancer, BRCA mutations can increase the risk of a second primary breast cancer (a second breast tumor that is unrelated to the first one). The chance of developing a second primary cancer ten years after diagnosis of the first cancer is about 30 percent for breast cancer survivors with a BRCA mutation (32 percent for BCRA1 mutation and 25 percent for BRCA2 mutation), compared to about 10 percent for survivors without mutations [17]. In young women with a BRCA mutation, the lifetime chance of a second primary tumor in the opposite breast may be as high as 60 percent [18].
BRCA Mutations & Risk of Ovarian Cancer
In addition to increasing the risk of breast cancer, BRCA mutations increase a woman's risk of ovarian cancer. A woman's chance of developing ovarian cancer by age 70 is about 1 to 2 percent if she does not have a BRCA1 or BRCA2 mutation [19], 39 to 63 percent if she has a BRCA1 mutation and 11 to 27 percent if she has a BRCA2 mutation [20]. Women with a BRCA mutation can reduce their risk of ovarian cancer by having prophylactic oophorectomy (surgical removal of the ovaries). For more on this, click here.
BRCA Mutations & Male Breast Cancer
Mutations in the BRCA genes are not exclusive to women. Men also carry the mutations, usually in the BRCA2 gene. These inherited mutations increase the risk of male breast cancer and may also raise the risk of prostate cancer [21-23]. 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 [21]. The lifetime risk of breast cancer is 1 in 1000 for average men and about 60 to 70 in 1000 for men with a BRCA1 or BRCA2 mutation [24,25].
For more on male breast cancer, click here.
For more information about genetic testing, click here.
For more on risk-reducing options for women at higher risk, click here.
Updated 09/12/09
