Breast cancer is a common disease. Each year, approximately 200,000 women in the United States are diagnosed with breast cancer, and one in nine American women will develop breast cancer in her lifetime. But hereditary breast cancer - caused by a mutant gene passed from parents to their children - is rare. Estimates of the incidence of hereditary breast cancer range from between 5 to 10 percent to as many as 27 percent of all breast cancers.
In 1994, the first gene associated with breast cancer - BRCA1 (for BReast CAncer1) was identified on chromosome 17. A year later, a second gene associated with breast cancer - BRCA2 - was discovered on chromosome 13. When individuals carry a mutated form of either BRCA1 or BRCA2, they have an increased risk of developing breast or ovarian cancer at some point in their lives. Children of parents with a BRCA1 or BRCA2 mutation have a 50 percent chance of inheriting the gene mutation.
In 1995 and 1996, studies of DNA samples revealed that Ashkenazi (Eastern European) Jews are 10 times more likely to have mutations in BRCA1 and BRCA 2 genes than the general population. Approximately 2.65 percent of the Ashkenazi Jewish population has a mutation in these genes, while only 0.2 percent of the general population carries these mutations.
Further research showed that three specific mutations in these genes accounted for 90 percent of the BRCA1 and BRCA2 variants within this ethnic group. This contrasts with hundreds of unique mutations of these two genes within the general population. However, despite the relatively high prevalence of these genetic mutations in Ashkenazi Jews, only seven percent of breast cancers in Ashkenazi women are caused by alterations in BRCA1 and BRCA2.
Not all hereditary breast cancers are caused by BRCA1 and BRCA2. In fact, researchers now believe that at least half of hereditary breast cancers are not linked to these genes. Scientists also now think that these remaining cases of hereditary breast cancer are not caused by another single, unidentified gene, but rather by many genes, each accounting for a small fraction of breast cancers. In Learning About the BRCAX Study, researchers discuss a recent advance in understanding hereditary breast cancer, and the challenges that remain.
Hereditary breast cancer is suspected when there is a strong family history of breast cancer: occurrences of the disease in at least three first or second-degree relatives (sisters, mothers, aunts). Currently the only tests available are DNA tests to determine whether an individual in such a high-risk family has a genetic mutation in the BRCA1 or BRCA2 genes.
When someone with a family history of breast cancer has been tested and found to have an altered BRCA1 or BRCA2 gene, the family is said to have a "known mutation." Positive test results only provide information about the risk of developing breast cancer. The test cannot tell a person whether or when cancer might develop. Many, but not all, women and some men who inherit an altered gene will develop breast cancer. Both men and women who inherit an altered gene, whether or not they develop cancer themselves, can pass the alteration on to their sons and daughters.
But even if the test is negative, the individual may still have a predisposition to hereditary breast cancer. Currently available technique can't identify all cancer-predisposing mutations in the BRCA1 and BRCA2 genes. Or, an individual may have inherited a mutation caused by other genes. And, because most cases of breast cancer are not hereditary, individuals may develop breast cancer whether or not a genetic mutation is present.
Given the limitations of testing for hereditary breast cancer, should an individual at high risk get tested? Genetic counselors can help individuals and families make decisions regarding testing.
For those who do test positive for the BRCA1 or BRCA2 gene, surveillance (mammography and clinical breast exams) can help detect the disease at an early stage. A woman who tests positive can also consider taking the drug tamoxifen, which has been found to reduce the risk of developing breast cancer by almost 50 percent in women at high risk. Clinical trials are now under way to determine whether another drug, raloxifene, is also effective in preventing breast cancer.
Currently, NHGRI is not conducting studies on Breast Cancer.
Last Updated: November 7, 2014
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