Genetic Testing for Breast Cancer Risk: It's Your Choice
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.
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
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.
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.
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
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.
What are the benefits of genetic testing for breast and ovarian
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.
What could happen if genetic test results are placed in medical
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.
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.
How much does testing cost and how long does it take to get the
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
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
- 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, August 1997