# Hereditary Breast and Ovarian Cancer Fact Sheet

Most breast cancer cases are sporadic and occur in individuals who do
not have a family history of breast or other cancers. Heredity probably
accounts for approximately 5-10% of breast and ovarian cancer cases
diagnosed annually in the United States.

-   In hereditary cancers, several members of an extended family are
    affected with the same or related types of cancer.

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-   In some families, breast cancer may be caused by mutations in an
    inherited susceptibility gene (i.e. BRCA1 or BRCA2). This means that
    a [mutation](../mutate.htm) in a single gene is being passed from
    generation to generation. Family members who inherit the gene
    mutation have a significantly increased risk of developing cancer.

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-   In families in which breast cancer is caused by an inherited
    mutation in a susceptibility gene, one or more of the following
    characteristics are common:

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-   there are usually three or more individuals with breast cancer in
    more than one generation.

-   the cancer may occur at younger-than-average ages (breast cancer
    younger than age 50)

-   bilateral breast cancer is more common.

-   individuals with breast cancer are more likely to develop a second
    cancer.

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-   It is important to realize that, with all of the recent and
    important discoveries about the [genetic and molecular basis of
    cancer](../gncavrvu.htm), many questions still remain unanswered as
    to why breast or ovarian cancers occur. Since most breast cancers
    are not due to hereditary causes, most women will not benefit from
    genetic testing.

Two major cancer susceptibility genes were discovered and given the
names, BRCA1 and BRCA2 (which stands for BReast CAncer 1 and 2) by
analyzing the genetic material of large, high-risk families. Recent
studies indicate that these two genes may account for less than 30% of
the genetic contribution responsible for heritable breast cancer; there
are other genes contributing to the predisposition of breast cancer.
BRCA1 and BRCA2 are thought to be tumor suppressor genes, which normally
act to control the growth of cells. The BRCA1 gene is located on
[chromosome](../chromos.htm) 17 and the BRCA2 gene is located on
chromosome 13. Men and women who carry a mutation in a copy of the BRCA1
or BRCA2 genes have a 50% chance of passing that mutation on to each of
their children.

By 1997, more than 200 different mutations were identified in BRCA1 and
BRCA2. Probability tables have been constructed to provide estimates of
the likelihood of finding a BRCA mutation in women with a family history
of breast cancer. More research is needed to examine gene mutations in
different ethnic and geographic groups. Research on individuals of
Ashkenazi (Eastern European) Jewish descent has shown that 2.5 percent
of this population will have a mutation in BRCA1 or BRCA2.

Genetic counseling is recommended for high-risk families considering
genetic testing. Counseling includes a review of the risks, benefits,
and limitations of genetic testing as well as a personalized assessment
of the probability of being a mutation carrier. In order to maximize the
likelihood of obtaining a useful and "informative" test result, it is
recommended that the first individual tested be the individual who has
been diagnosed with early onset breast cancer or ovarian cancer. When
someone with a cancer diagnosis ***and*** a family history of the
disease has been tested and found to have a mutation in BRCA1 or BRCA2,
the family is said to have a \"known mutation.\" Others in the family
can be tested to see if they have that specific mutation. Risks for
insurance and employment discrimination must be considered before
undergoing genetic testing.

A positive test result indicates that a woman 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. A negative test result in a family with a known mutation will
mean that the tested individual is not at an increased risk for
developing cancer. In a family where a mutation has not been identified,
a negative test result will be "uninformative". In this situation, there
is the potential for the tested individual to be falsely reassured and
to relax screening practices.

In addition, evidence from several studies has shown that a man with a
mutation in BRCA1 or BRCA2 has a small increased risk for developing
prostate cancer. A man with a mutation in BRCA2 has an increased risk
(about 6 percent) for breast cancer and may be at increased risk for
other cancers. 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.

According to lifetime risk estimates for women in the general
population, about 12% (1 in 8 women) will develop breast cancer,
compared with an estimated 50 to 85% of women with mutations in the
BRCA1 or BRCA2 genes. Lifetime risk estimates for women in the general
population predict that 1.5% (1 in 70 women) will develop ovarian
cancer, compared with an estimated 40-60% of women with mutations in
BRCA1 and 10-15% of women with mutations in BRCA2.

Early estimates of the risk of breast cancer in a woman who carries a
BRCA1 or BRCA2 mutation may have been artificially high as they were
based on families with multiple cases of breast or ovarian cancer, or
both. Research continues to identify other cancers that may be
associated with BRCA1 and BRCA2 mutations. Pancreatic cancer, lymphoma,
multiple myeloma, Hodgkin's disease, and lung cancer have been shown to
be more common among families of BRCA carriers.

If an individual has been found to have a BRCA1 or BRCA2 mutation,
additional screening may be indicated. The following screening
guidelines for mutation carriers are based largely upon expert opinion.

-   For women, monthly breast self-exams (BSE) starting at age 18-21,
    annual clinical breast exams (CBE) starting at age 25-35, and annual
    mammography starting at age 25-35

-   For women, annual clinical pelvic exams starting at age 25-35,
    annual serum CA-125 starting at age 25-35, and annual transvaginal
    ultrasound starting at age 25-35 (\*benefit of ovarian cancer
    screening is unproven)

-   For men, annual serum prostate specific antigen (PSA) starting at
    age 50 (\*benefit of prostate cancer screening is unproven)

-   For men and women, annual digital rectal exam (DRE), annual fecal
    occult blood test, and flexible sigmoidoscopy every 3-5 years,
    starting at age 50

Individuals with mutations in BRCA1 and BRCA2 should also be offered
counseling about the risks, benefits, and limitations of other
management options including prophylactic surgery, chemoprevention, and
lifestyle modifications.