Download So what can be done if you have a genetic mutation? There are 3

HEREDITARY BREAST AND OVARIAN CANCER
Lila Courtney,ARNP-c,AOCN
Two cancer susceptible genes, BRCA 1 and BRCA 2, have been identified for hereditary breast and ovarian cancer. As a result, we can now test to see if a person carries these mutations and what can be done to prevent both cancers. It is important to remember that a majority of cancers occur sporadically, about 60%. Thirty percent of cases are thought to be familial, and only 10% are thought to be truly hereditary. Cancer arises from an uncontrolled growth of cells. Cells are units that make up our tissues and organs, which in turn make up our entire body. When cells are doing their jot well, they know how to grow and when to stop growing. Cells contain genes. Genes carry the instructions that tell cells how to function properly, when to grow and when to stop. Some cancers are caused by harmful changes in genes called mutations. These mutations cause the cells to grow without control and eventually
become a cancer. Hereditary susceptibility to cancer can be inherited and passed on within a family. When a person has hereditary cancer susceptibility, he or she has inherited a copy of a cancer susceptible gene with a mutation from one parent and a working copy of the same gene from the other parent. Individuals who inherit a mutation of a cancer-susceptible gene (BRCA 1 or BRCA 2) have a much greater chance of developing cancer. However, it is important to know that not everyone with a cancer susceptible gene mutation will develop cancer. There are certain "red flags" that have been identified that alert us to the possibility that they may
have a gene mutations. We look at their personal history of cancer as well as family history, both maternal and paternal. These "red flags" include breast cancer before age 50; ovarian cancer at any
age; male breast cancer; multiple primary cancers; Ashkenazi Jewish ancestry; or relatives of a BRCA mutation carrier. If you have a BRCA mutation, you have an increased risk for developing a cancer compared to the general population. It is important to remember that it is not a 100% risk of developing cancer. You have a 50% risk of developing breast cancer by age 50; an 87% risk of developing breast cancer by
age 70; and a 44% chance if developing ovarian cancer by age 70. Having a mutation can also increase your risk for a second cancer: 16% risk of developing ovarian cancer after a breast cancer; and a 64% risk of developing a second breast cancer by age 70.
So what can be done if you have a genetic mutation? There are 3 tiers of management options
that can be used to improve outcomes. The first level is increased surveillance. Monthly selfbreast exams should start between ages 18-21, annual or semiannual clinical breast exam,
beginning between ages 25-35, and yearly mammograms beginning between ages 25-35. For
ovarian cancer, there are no good screening options. The two options that are available are
annual or semiannual transvaginal ultrasound and a CA-125 tumor marker. Of interest, the CA125 is not always elevated in ovarian cancer.
The next tier is chemoprevention. That is where you can take medication to reduce your risk for
developing cancer. Tamoxifen has been shown to reduce the risk of breast cancer. For an unaffected
high-risk person it can reduce the risk by 45%; for an unaffected BRCA 2 carrier, it can reduce risk
by 62%; and for an affected BRCA carrier it can reduce the risk for a contra lateral breast cancer by
75%. For ovarian cancer prevention, oral contraceptives taken for greater than 6 years can reduce the
risk by 60%.
The third tier is preventative surgery. Preventive mastectomy reduces the risk of breast cancer by
90%. Preventative removal of the ovaries in women with BRCA I or BRCA 2 mutation can reduce
the risk of ovarian cancer by 96% and removal of the ovaries can reduce the risk of breast cancer by
53%. Since there is not a good screening test for ovarian cancer, there is a recommendation to do
bilateral salpingo-oophorectomy (BSO) after childbearing is over or at age 35.
For male BRCA carriers, the recommendation for medical management is monthly breast exams
and yearly clinical breast exam. Mammography is done based on clinical findings. PSA (prostate
specific antigen) testing should be done yearly as well as a yearly digital rectal exam.
The American Society of Clinical Oncology has established guidelines for genetic testing. The
guidelines are personal or family history suggestive of hereditary cancer risk, the test must be able to
be interpreted, and the test results will aid in the diagnosis or influences medical management of the
patient and family.
The genetic test is done by a blood draw. The first person in a family to be tested need a
comprehensive analysis which is full sequencing of BRCA 1 or BRCA 2 genes and a panel of large
rearrangements for hereditary breast and ovarian cancer. As of now, 84% of all hereditary breast and
ovarian cancers are caused by the BRCA 1 and BRCA2 genes. There may be other genes that we do
not know about and therefore cannot test for. If a person has a positive result and a mutation of
BRCA 1 or BRCA 2 is identified, their blood relative can then be tested for the single site BRCA
analysis.
There are several possible genetic test results. A positive result means the mutation of BRCA 1 or
BRCA 2 was found and the person is at increased risk for developing breast and/or ovarian. A
negative result means no mutation was found. It is a true negative if there is a known BRCA
mutation in the family and if the person did not inherit the mutation they therefore cannot pass it on
the their children. You can also get an uncertain variant result. This means there is an abnormality
found but the abnormality has not been linked to any particular cancer. At this point in time we do
not know of a cancer link to this abnormality.
Before a genetic blood test is drawn its important to discuss that the results not only affect the person
being tested but other people who are blood related to them. All first-degree relative- parents,
children, brothers, and sisters have up to a 50% chance that they carry the same mutation. Other
relative may be at lesser risk to carry the same mutation.
Genetic testing offers benefits because it can allow for individualized risk assessment and provide
appropriate medical management for mutation carriers. Some insurance companies cover the cost of
the test and Medicare covers it 100% if certain criteria is met. Knowing your accurate risk and what
can be done to prevent a cancer can alleviate uncertainty and anxiety.
There are limitations also with genetic testing. The most informative results are positive and true
negative. Also genetic testing for BRCA I and BRCA 2 does not identify all causes of hereditary
breast and ovarian cancer.
People are concerned about discrimination from health insurance companies if they get a genetic test.
To date over 50,000 clinical test have been performed and there has been no well-documented cases
of genetic discrimination. Federal and state laws prohibit the use of genetic information as a "preexisting condition". State laws vary so you must check what your state protects. HIP AA, which is a
federal law, protects individual’s in-group health plans by prohibiting the use of genetic test results to
determine eligibility or rate/cost of health insurance.
The world of genetics is opening up and in years to come hopefully will help us answers many
questions we now have about hereditary cancers. We will possibly know of more mutations that are
linked to cancer and what we can do to prevent the cancers. Genetics is indeed an exciting science.