Genetic Testing for Breast Cancer Risk

A woman and her doctor going over genetic testing results for breast cancer.

Breast cancer is the most commonly diagnosed form of cancer, except for cancers of the skin, and the second most common cause of cancer death for American women. Each year, more than 180,000 women learn they have a diagnosis of breast cancer. Approximately 5 to 10 percent of women with breast cancer have a hereditary form of the disease. It is believed that inherited alterations (called mutations) in the BRCA1 and BRCA2 genes are involved in 30 to 70 percent of all inherited cases of breast cancer; the likelihood is highest in families with one or more cases of ovarian cancer.

Since the vast majority of breast cancer cases are not due to inherited alterations in the BRCA1 or BRCA2 genes, most women would not benefit from genetic testing. For men and women with a family history of breast and ovarian cancer, genetic testing may indicate whether they have an increased chance of developing breast cancer. There are, however, many things to think about before getting tested.

  1. How do alterations in BRCA1 and BRCA2 affect a woman's risk for breast and ovarian cancers?

    A woman's lifetime susceptibility to breast and ovarian cancers is substantially elevated if she inherits an altered BRCA1 or BRCA2 gene. Women who have inherited these gene alterations usually have an increased risk of developing breast cancer at a younger age (before menopause), and they often have multiple close family members with the disease. Because most research has been conducted with large families with many affected individuals (cancer patients), the estimates generally cited for the risk of developing breast and/or ovarian cancers in women carrying altered BRCA1 and BRCA2 genes may be artificially high. Recent studies of groups more representative of the general population have found somewhat lower risk figures for the diseases. Therefore, figures for breast and/or ovarian cancer risk in persons with altered BRCA1 and BRCA2 genes should be viewed as broad ranges that may change as more research data are added.

    According to lifetime risk estimates for women in the general population, about 12 percent (120 out of 1000 individuals) will develop breast cancer, compared with 50 to 85 percent (500-850 out of 1000) of women with an altered BRCA1 or BRCA2 gene. The risk for some women may be lower. For ovarian cancer, lifetime risk estimates for women in the general population predict that 1.5 percent (15 out of 1000) will get ovarian cancer, compared with 5 to 40 percent (50-400 out of 1000) for women with an altered BRCA1 gene, and 10 to 20 percent (100-200 out of 1000) for women with an altered BRCA2 gene.

    These broad ranges of risk estimates reflect the fact that actual risks will differ from one person to another. Although these estimates can be useful for considering risk in large groups of people, currently they cannot provide a precise cancer risk for an individual.

  2. Does the frequency of alterations in BRCA1 and BRCA2 vary in different ethnic populations?

    Specific gene alterations have been identified in different ethnic and geographic groups. For example, among individuals of Ashkenazi (Eastern European) Jewish descent, 2.5 percent (20 out of 800 persons) will have an altered BRCA1 or BRCA2 gene. This is significantly more common than in the general population, where about 1 in 800 individuals (about 0.1 percent) will have an alteration in BRCA1 or BRCA2. Three particular mutations have been found in the Ashkenazi Jewish population: two in the BRCA1 gene and one in the BRCA2 gene. Currently, it is not known whether these are the only mutations that frequently occur in these populations, nor is it known whether breast cancer is more prevalent in the Ashkenazi Jewish population than in the general population. Researchers continue to investigate genetic alterations that may affect breast cancer risk in other ethnic and geographic populations, for example, in Norwegians and Icelanders.

  3. What does a positive BRCA1 or BRCA2 test result mean?

    When someone with a cancer diagnosis and a family history of the disease has been tested and found to have an altered BRCA1 or BRCA2 gene, the family is said to have a "known mutation." Others in the family can be tested to see if they have that mutation. A positive test result indicates that a person has inherited a known BRCA1 or BRCA2 gene alteration and has an increased risk of breast and ovarian cancer. However, a positive result only provides risk information and cannot tell a person whether or when cancer might develop. It is also impossible to predict how a woman will respond to medical treatment should cancer be diagnosed. It is important to note that many but not all women who inherit an altered gene will develop breast or ovarian cancer.

    In addition, evidence from several studies has shown that a man with an altered BRCA1 or BRCA2 gene has a small increased risk for developing prostate cancer. A man with an altered BRCA2 gene has an increased risk (about 6 percent) for breast cancer and may be at increased risk for other cancers. (Only a few men with breast cancer have been found to carry an altered BRCA1 gene.) Both men and women who inherit an altered gene, whether or not they get cancer themselves, can pass the alteration on to their sons and daughters.

  4. What does a negative BRCA1 or BRCA2 test result mean?

    A negative test result will be interpreted differently, depending upon whether a family alteration is known. If a known mutation is not found in certain family members, those individuals do not have a strong risk for breast cancer based on family history and cannot pass the family risk on to their children. In cases where no BRCA1 or BRCA2 alteration has previously been identified in a family, a negative test is not very informative. It is not possible to tell whether a person actually does have an alteration but the test missed it (false negative), or whether the result is a true negative. Further, a woman may have an alteration in a gene other than BRCA1 or BRCA2 that increases her cancer risk but is not detectable by this test.

    If the test finds an alteration that has never been seen before in anyone else, the risk of cancer for that person may be uncertain. Everyone has alterations in some of their genes that do not increase their risk of disease; this type of alteration is called a "silent polymorphism." In addition, breast cancer is an extremely common disease in the population, and the vast majority of women diagnosed with this disease do not have an inherited tendency; so even women with a negative test result should be aware that they can get breast cancer.

  5. What are the options for a person who tests positive?

    Several approaches may be taken in managing cancer risk in those individuals who have been found to have a mutation in a BRCA1 or BRCA2 gene. These are:

  • Surveillance. If cancer develops, it is important to detect it as soon as possible. Even with careful surveillance, not all cancers will be diagnosed early enough to be successfully treated. Nonetheless, careful monitoring for symptoms of cancer is considered important. Surveillance methods for breast cancer may include mammography and a clinical breast exam; some health professionals recommend breast self-exams, but this should not be used to replace clinical exams. For ovarian cancer, surveillance methods may include pelvic ultrasound, CA-125 blood testing, and clinical exams. Surveillance can sometimes pick up cancer at an early stage, but it does not guarantee a cure if cancer is found.
  • Prophylactic Surgery. This type of surgery entails the removal of as much of the at-risk tissue as possible in order to reduce the chances of developing cancer. Preventive mastectomy (removal of healthy breasts) and oophorectomy (removal of healthy ovaries) do not, however, offer a guarantee against developing cancer. Some women have developed breast or ovarian cancer after prophylactic surgery.
  • Risk Avoidance. Particular behaviors that are believed to decrease cancer risk include limiting alcohol consumption and increasing regular exercise. Research results on the benefits of these behaviors are based on studies in the general population; the effects of these actions on BRCA1 and BRCA2 mutation carriers are unknown.
  • Chemoprevention. This approach involves the use of medication, such as tamoxifen, and micronutrients like dietary retinoids, vitamin E, and selenium. Tamoxifen is a drug used to prevent a recurrence of cancer in women who have already been diagnosed with cancer. In these women, tamoxifen also has been found to prevent new cancers from developing in the other breast. Studies are currently under way to determine whether high-risk women in the general population can benefit from taking tamoxifen as a prevention for breast cancer, and several other chemoprevention studies and clinical trials that involve carriers of an altered BRCA1 or BRCA2 gene are anticipated.
  • Gene Therapy. At present, altered genes cannot be repaired. Some day it may be possible to fix or manipulate the genes or sets of genes that cause or increase one's risk for cancer and other illnesses.
  1. What are the benefits of genetic testing for breast and ovarian cancer risk?

    For some women, the benefits of genetic testing include the ability to make medical and lifestyle decisions while reducing the anxiety of not knowing their genetic background. Another benefit is the ability to make a proactive decision concerning prophylactic surgery. In addition, many women are able to participate in medical research that may, in the long run, decrease the risk of death from breast cancer.

  2. What could happen if genetic test results are placed in medical records?

    The inclusion of genetic test results in a patient's records may have serious implications. For example, in the process of applying for medical, life, or disability insurance, a patient may be asked to sign forms that give an insurance company permission to access medical records. If this is the case, and an insurance company accesses that individual's medical records, the test results may affect the applicant's ability to get insurance. Individuals considering genetic testing must understand that when test results are placed in their medical records, the results might not be kept private.

    Some physicians may be willing to keep test results out of medical records. Patients who decide to have genetic testing should be informed that the results can sometimes be kept out of the person's records, particularly if the testing is performed as part of a research study. However, there would still be some risk for discrimination. For example, a woman found to have an altered BRCA1 gene may not be able to justify the need for increased surveillance or prophylactic surgery without divulging this information to her insurance company. Sometimes, these procedures may be approved by an insurance company based on family history information, so it may not always be necessary to reveal genetic testing results.

  3. What are the risks for insurance and employment discrimination?

    If a genetic alteration is found that increases the risk for developing cancer, it could affect the status of a person's health, life, and disability insurance by causing that individual to be unable to qualify for new insurance, increasing premium payments, or decreasing the amount of coverage. Some insurers view the affected individual as a potential cancer patient whose medical treatment would be costly to the insurance company.

    A patient who tests positive for a BRCA1 or BRCA2 mutation may also experience employment discrimination if an employer learns about the test result. Some protection from discrimination by employers is offered through the Americans with Disabilities Act (ADA). Recently, the Equal Employment Opportunity Commission (EEOC) expanded the definition of "disabled" to include individuals who carry genes that put them at higher risk for genetic disorders. The extent of this protection, however, has not yet been tested in the courts.

    Once an individual learns his or her genetic test results, insurance companies and employers may have access to this information simply by asking the person to provide the information to them. If an individual fails to provide truthful information, it is considered fraud and may result in loss of insurance coverage or employment. Around the country, efforts are under way to prevent insurance and employment discrimination. It should be noted that the degree of discrimination protection can vary from state to state. Therefore, individuals considering testing should be reminded that the decisions that they make today while living in one state may have repercussions in the future if they move to another area.

  4. How much does testing cost and how long does it take to get the results?

    The cost for genetic testing can range from several hundred to several thousand dollars. Insurance policies vary with regard to whether the cost of genetic testing is covered.

    As addressed above, because genetic information can cause problems with insurance companies, some individuals may not want to use their insurance to pay for testing and may choose to pay out of pocket if they are able. This may be true even when a particular insurer is willing to cover the cost of testing. To protect their privacy, some may not even want their insurer to know they are thinking about genetic testing. Others may decide to ask their insurance company to cover these costs. They should carefully explore their particular insurance company and even privacy protection laws in their state before submitting the charge.

    From the date that blood is drawn, the availability of test results can take several weeks or months. The length of time that it takes to get test results depends on the tests performed and under what circumstances they are done. Individuals who decide to get tested should check with their doctor or a genetic counselor for more information about when test results might be available.

  5. Besides inherited gene alterations, what other factors are believed to affect the risk of breast and ovarian cancers?

    The following factors may be associated with breast cancer risk in the general population. It is not yet known how these factors influence risk in carriers of BRCA1 or BRCA2 mutations.

  • Age. The risk for breast cancer increases with age. Eighty percent of cases occur in women older than age 50. (However, women with an altered BRCA1 or BRCA2 gene often develop breast cancer before age 50.)
  • Medical History. Women who have already had breast or ovarian cancer may be at increased risk for developing additional cancers.
  • Hormonal Influences. Estrogen stimulates the normal growth of breast tissue and is naturally produced by the body. It is suspected that excess estrogen may contribute to breast cancer risk because of its natural role in stimulating breast cell growth. Removal of a woman's ovaries (artificial menopause), and the estrogen that ovaries produce, clearly reduces her risk for breast cancer. And women who have had their first menstrual period before age 12 or enter menopause after age 55 have a slightly increased risk of breast cancer as do women who have had their first child after age 30.
  • Birth Control Pills. Most studies show a slight or no increase in breast cancer risk in women taking birth control pills, but a decreased risk for ovarian cancer. Some studies suggest that a woman who has taken birth control pills for more than 8 years, and began taking them at an early age or before her first pregnancy, has a small increase in her risk for breast cancer.
  • Hormone Replacement Therapy. A woman's risk for breast cancer may be increased by hormone replacement therapy (HRT) when used for more than 10 years. HRT also may have protective effects, such as lowering a woman's risk for heart disease and osteoporosis. However, the protective effects diminish within several years after a woman discontinues therapy.
  • Dietary Fat. Although early studies suggested a possible association between a high-fat diet and increased breast cancer risk, more recent studies found that reduced dietary fat consumption did not decrease risk of breast cancer.
  • Physical Activity. Studies of the relationship between physical activity and breast cancer have had mixed results, but some studies suggest that regular exercise may decrease breast cancer risk.
  • Alcohol. There may be a small increase in breast cancer risk due to alcohol consumption, but studies have been inconsistent. Alcohol may indirectly increase estrogen levels, but no biological mechanism for the relationship between alcohol and breast cancer risk has been established.
  • Environmental Factors. Exposure of the breast to ionizing radiation is associated with an increased risk of breast cancer, especially when the exposure occurs at a young age. Evidence examining the effect of occupational, environmental, or chemical exposures on breast cancer risk is limited. For example, there is some evidence to suggest that organochlorine residues in the environment such as those from insecticides might be associated with an increase in breast cancer risk, but the significance of this evidence has been debated. Scientific research is currently in progress to study the effects of various environmental factors on breast cancer risk.

A person who is considering genetic testing should speak with a professional trained in genetics before deciding whether to be tested. For more information on genetic testing or for a referral to centers that have health care professionals trained in genetics, call the National Cancer Institute's Cancer Information Service at 1-800-4-CANCER. The Cancer Information Service can also provide information about clinical trials and research studies.

Source: National Action Plan on Breast Cancer

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