Family History and Genetic Risk
Does having a family history of breast cancer increase the risk of breast cancer?
Most women -- especially younger women -- believe that their own risk of developing breast cancer is higher than it actually is. Those with a family history of breast cancer also guess that their risk is much higher than it really is. A family history of breast cancer is the risk factor most known by women.
Of all the women whose close relatives have had breast cancer, 80–90% are at no particular extra risk themselves; 5–15% have a familial (but not hereditary) risk that is somewhat elevated-but not by much; and five percent may be carriers of one of the specific gene mutations known to result in a high lifetime risk of breast and ovarian cancer.
How does family history affect the risk of breast cancer?
Women who have a mother or sister (or both) who has had breast cancer have different types and amounts of risk.
- Those at risk of hereditary breast cancer
An extremely small fraction of women have specific mutations on genes called the BRCA1 (breast cancer 1) or BRCA2 gene. Because of this mutation, the genes are unable to function properly in suppressing the growth of tumors. As a result, the risk of breast cancer is higher. Other genes or gene pathways that affect risk may be discovered in the future. Women who have inherited a mutated gene are the only ones who are at risk of what is called hereditary breast cancer. - Those at risk of familial breast cancer
A larger group of women may be at a moderately higher risk of familial breast cancer. In these families, breast cancer affects one's relatives across several generations at an above-average rate, but no specific cancer-related genes are known to be involved. The somewhat higher risk could be related to factors that are partially inherited, such as body size, a tendency to gain weight during middle age, or a higher general level of circulating (natural) estrogens. This increased risk could also be related to factors that are socially rather than biologically inherited, such as preference of family size, acceptable age for childbearing, and even food choices. - Those with no associated risk
Between 80% and 90% of women whose mothers or sisters had breast cancer are at no particular extra risk of breast cancer themselves. Most breast cancers have little to do with inherited factors. If your sister or mother had breast cancer after menopause, there is a lower likelihood that you will be at higher risk yourself. More than 90% of breast cancers in women over age 45 are not connected to heredity, genetic risk, or family history at all.
Who is likely to be a carrier of a BRCA1 or BRCA2 mutation?
In the United States, the group that has the highest known frequency of BRCA1 or BRCA2 gene mutations is the Ashkenazi population. The term generally refers to Jewish families that trace their heritage from central and eastern Europe. Approximately two percent of Ashkenazi Jewish men and women are affected by one of three specific breast cancer gene mutations that predispose them to breast cancer. According to a large study conducted in Washington, D.C., Ashkenazi women who carry one of the cancer-associated genes may have a 33% risk of having breast cancer by age 50 and a 56% risk by age 70. Other studies of Ashkenazi residents of Baltimore and New York City estimate a lifetime breast cancer risk of 35% (three times the average risk) for carriers of the BRCA1 or BRCA2 gene mutations. A high incidence of BRCA2 mutations has been found among women of Icelandic descent as well. Breast cancer mutations can also run in specific families from any cultural background or geographic region.
In the United States, cancer-associated gene mutations are extremely rare, affecting perhaps one woman in 1,000. Even among women who have had breast cancer, fewer than five percent have BRCA mutations. And even among women who had breast cancer before age 35, these mutations are uncommon, affecting only 5–10%. A woman who has never had breast cancer but has both a mother and either a grandmother or aunt who developed breast cancer before the age of 45 would have a 5–10% chance of carrying a cancer-associated gene mutation herself. However, if only one close relative (either a mother or sister) had breast cancer before age 45, a woman's chance of carrying a cancer-associated gene mutation would be under three percent.
Will all women who carry the gene mutation get breast cancer?
Until very recently, estimates of the risk of hereditary cancer were based on small studies of a few families that had an extraordinarily high rate of breast and ovarian cancer. These families often had 5–10 cases of breast cancer within two or three generations. Not surprisingly, the resulting estimates for the risk of breast cancer were also very high: the lifetime risk was as much as 80–90%. Until studies on larger populations were completed, the 80% figure was used as a risk estimate for women who carried the BRCA1 or BRCA2 gene mutations, even if they were not members of such high-risk families and had only three or four affected relatives.
Larger study groups of community populations showed that the 80% figure was an overestimate. For example, women in Iceland have a particularly high rate of one of the BRCA2 mutations: as many as six women in 1,000 are affected. Women who carry this mutation have a 17% chance of getting breast cancer before age 50 and a 37% chance by age 70. Although this is an extremely high risk when compared with the risk for women who do not have the mutation, the figure is still nowhere near 80%.
What should a woman do if she thinks she may have a genetic risk of breast cancer?
If you believe that hereditary breast and ovarian cancer may run in your family, the first step is to learn more about familial cancers, about where to locate genetic counseling centers, and about the pros and cons of genetic testing. This Web site is a useful place to begin: Genetic Testing for BRCA1 and BRCA2: It's Your Choice.
Note that this information is based on pre-1998 estimates of the lifetime risk of breast cancer for women who have genetic mutations. Whenever the text reads 80–90%, substitute the more recent and accurate estimate of 35–50%.
How accurate is genetic testing in assessing risk?
Genetic testing is highly controversial. It is important to remember that genetic tests are not 100% accurate: as many as 30% of BRCA1 and BRCA2 mutations are not identified by tests. More than 200 different kinds of mutations have already been identified in BRCA1 and 2 genes, and only a very few of these are known to be connected to the risk of breast cancer. Hence, in order to determine whether a BRCA mutation increases the risk of breast cancer for a particular individual, it is necessary to conduct family tests in which the individuals diagnosed with breast or ovarian cancer are tested for particular mutations.
Who might consider having a genetic test for a cancer gene mutation?
Genetic testing is a process for families, not for individual women. Because there are so many BRCA1 and 2 mutations, it is important to investigate a particular mutation over generations and to identify its connection to the incidence of breast or ovarian cancer in that family. Families that might wish to consider genetic counseling -- a necessary first step before genetic testing -- include those with four or more women who have had breast or ovarian cancer across at least two generations; those with a blood relative who has had both breast and ovarian cancer; or those with male relatives who have had breast cancer. A woman who was diagnosed with breast or ovarian cancer before age 45 might want genetic counseling, even if she had only a few relatives with a history of the disease, because of the possibility of a rare genetic problem that could affect her sisters and children (of either sex). Remember, too, that genetic counseling is available to any woman who is concerned about her own risk of familial breast cancer, even if she has only one or two affected relatives and is probably at very low risk of hereditary cancer.
What are the benefits of genetic testing?
If you are considering a genetic test, keep the following points in mind. Before getting a genetic test for a cancer gene, or any diagnostic test for that matter, ask yourself if anything would be different if the test result was one outcome as opposed to another.
If you are one of the few women with a cancer-associated gene mutation, you would probably be advised to get a physical breast examination and a mammogram annually. If you are already doing that, getting a genetic test will probably not change what you do already.
Some women who have a strong family history of breast cancer have chosen to undergo very radical procedures to reduce their risk -- having their breasts and/or ovaries surgically removed. If you are considering such an option, you may well want to have the test in order to find out if your personal risk is above average or not.
The professional groups that provide or evaluate genetic testing for breast cancer are unanimous in recommending that such testing not be undertaken without genetic counseling before and after the testing process. The interpretation of test results is complicated and requires specialized training to explain what the results do or do not mean for an individual woman. If you are considering genetic testing, your primary care doctor has probably not been trained to advise you. Look for a specialized genetic counseling center.
What can be learned from consulting a genetics counselor?
At the initial counseling session, women learn about some of the non-medical risks associated with genetic testing. Most women who seek genetic counseling about the risk of familial breast cancer learn that there is no reason for them to get genetic testing.
Genetic testing has significant effects and should not be undertaken lightly. On the one hand, learning that you don't have a breast cancer gene mutation can be a relief. You can quit worrying about a high personal risk of breast cancer and know you have the usual average risk. On the other hand, genetic testing has significant risks. Having a test -- whether the outcome is positive or negative -- could affect your ability to get health or life insurance coverage in the future. Be sure to ask about this.
If a woman decides to have genetic testing, what should she expect?
The first step is to test a relative who has a history of breast or ovarian cancer for all known mutations on the BRCA1 and 2 genes. Then, if a cancer-associated gene mutation is identified, the woman's sisters or daughters can be tested for that particular gene mutation. The complete screening costs around $2,500 and is not generally covered by health insurance. The test for a single family-associated mutation costs around $400–$500. On average, half of the sisters and daughters of a cancer patient who has a gene mutation will have the same mutation, and half will not.
