How common are breast and ovarian cancers?
One in every nine women (about 11% of women) will be diagnosed with breast cancer at some point in her life. Breast cancer is the second most common type of cancer diagnosed among women — skin cancer tops the list.
An average woman's risk of ovarian cancer is about 1% to 2% (about one in 70). Ovarian cancer is more difficult to detect than breast cancer and is much harder to treat because it tends to be found after it has spread.
In the United States, 10% to 20% of women with breast cancer and 10% to 20% of women with ovarian cancer have a first-degree or second-degree relative with one of these cancers. A mother or sister is a first-degree relative. An aunt or grandmother is a second-degree relative. So far, research on inherited breast and ovarian cancer has focused on two genes — BRCA1 and BRCA2. However, these two genes only explain a proportion of all breast and ovarian cancer. For example, changes in the BRCA 1 and BRCA2 genes account for only 2% to 3% of all breast cancers. This means that other genes are contributing to familial breast cancer. Researchers continue to look for these other genes.
In the 1990s, mutations in two genes, BRCA1 (BReast CAncer 1) and BRCA2 (BReast CAncer 2), were shown to be involved in inherited breast and ovarian cancers. It is estimated that 40% to 90% of families with an inherited form of breast or ovarian cancer have a defective copy of the BRCA1 or BRCA2 gene.
BRCA1 and BRCA2 are called "tumor suppressor genes" because they make proteins that help prevent the cells from forming tumors. If one of these genes is changed through a mutation, the protein may not do its job, making it easier for a tumor to develop. Women who inherit a mutated copy of either the BRCA1 or BRCA2 gene have an increased chance of developing breast or ovarian cancer. In addition, there may be an increased risk for other cancers.
|Cancer risks associated with BRCA1|
|Breast Cancer Before Age 85||Ovarian Cancer Before Age 85|
|2 normal BRCA1 genes||11% risk||1%-2% risk|
|An altered BRCA1 gene||50%-85% risk||20%-40% risk|
|2 normal BRCA1 genes||about 0.1%||not applicable|
|An altered BRCA1 gene||‹6% by age 70||not applicable|
|Cancer risks associated with BRCA2|
|Breast Cancer Before Age 85||Ovarian Cancer Before Age 85|
|2 normal BRCA2 genes||11% risk||1%-2% risk|
|An altered BRCA2 gene||50%-85% risk||10%-20% risk|
|2 normal BRCA2 genes||0.1% risk||not applicable|
|An altered BRCA2 gene||‹6% by age 70||not applicable|
Does everyone with an altered BRCA1 or BRCA2 gene develop cancer?
No, not all women who inherit a mutated BRCA1 or BRCA2 gene will develop cancer. Among every 100 women with an altered BRCA1 or BRCA2 gene, 50 to 85 of them will develop breast cancer, compared with about 11 of every 100 women who do not have the altered gene.
It is not always clear why some women with BRCA1/BRCA2 mutations develop cancer and others do not. Some women choose to have breast and ovarian tissue surgically removed as a preventive measure. This decreases, but does not eliminate, the risk of developing cancer.
You are most likely to be at risk for inherited breast or ovarian cancer if you have a family history of one or both of these diseases. Meeting with a genetic counselor or a doctor trained in genetics will help you decide if genetic testing is right for you.
Do other genes contribute to inherited breast cancer?
Changes in the BRCA1 and BRCA2 genes only account for 2% to 3% of all breast cancers. Recently, another cancer gene, CHEK2, has been associated with breast cancer. A specific change in this gene — the 1100delC change — doubles the risk of breast cancer in women and a causes a 10-fold increase in risk for men. As time goes on, researchers will find more genes to explain inherited cancer risks.
Why does a genetic counselor need my medical records?
Medical records can be very helpful to your genetic counselor or doctor. Medical records of family members who have had breast cancer at younger ages or ovarian cancer are particularly helpful. The family member who had cancer (or his/her next of kin) will need to sign a medical record consent form from the hospital where he or she was treated to get the records released to you. Sometimes medical records are not available on family members who died a long time ago, but it may be possible to get a death certificate from the town or state where they lived.
How does my family history affect my health?
Your genetic counselor or doctor will ask you about your family history, so collect as much information as possible before you meet. Include information on all your relatives, not just the people who have had cancer.
Try to gather this information:
If you are adopted or part of your family history is unknown, your genetic counselor will work with whatever information you have available.
What does a genetic counselor or doctor look for in my family history?
A number of things, including:
Should I be the one tested in my family?
Not necessarily. Rather than testing you, your genetic counselor or doctor might recommend testing a relative who:
If you have a relative who falls into one of these categories, he or she will have the greatest chance of testing positive for a mutated BRCA1 or BRCA2 gene. If for some reason this relative cannot be tested, a family member (you, perhaps) who has not been diagnosed with cancer can be tested.
What if a family member has tested positive for BRCA1 or BRCA2?
In this case, testing you becomes simpler because your genetic counselor or doctor will know to look for the same mutation that was found in your family member. If you are tested and found to have the same mutation, you will know you are at increased risk for breast and ovarian cancer.
If your result is negative, it is very reassuring. This means that you do not have an increased risk for cancer and would not need more screening than a woman of your age and personal history. You can, of course, still develop cancer and you still need to be monitored appropriately, but you do not have the very high risks for breast and ovarian cancers, often developing at young ages, seen with these altered genes. Because the mutations don't "skip" generations, you also cannot pass on the altered gene to your children.
There are certain exceptions to this. For instance, if you have a strong family history of cancer on both sides of your family (your mom's side and your dad's side), it is possible that both sides have a BRCA mutation. Knowing you are negative for the BRCA1 or BRCA2 mutation from one side of your family does not rule out increased risk from the other side. Your genetic counselor should be able to review this with you in more detail.
What Testing Tells You
How do I make sense of my test results?
Although it is "just a blood test," the implications and results of a genetic test are not always black and white. Even for a woman who has survived breast or ovarian cancer, the test may not be as clear as she thinks.
Here are the possible test results:
A positive test result means that you have a mutation in BCA1 or BRCA2. This means you have an increased risk for cancer. However, the test cannot tell you if or when you will develop cancer or a second cancer. Although the risk is high, some women with these mutated genes never develop cancer during their lifetime.
At this time, there is no standard course of action to take once someone finds out that he or she has a BRCA1 or BRCA2 mutation. Most experts agree that intensive cancer screening should start at young ages. Prophylactic mastectomy and/or oophorectomy and chemoprevention are possible courses of action. Each person should discuss the advantages and disadvantages of each strategy with their physician to make the best decisions about managing this risk.
As far as researchers know, there are no true "false positives" without lab error. A "false positive" could happen if two samples were somehow switched either before or after the laboratory received them. It is important to make sure that the laboratory that performs the test is reputable and is certified to perform the test. There should be mechanisms in place to prevent these kinds of errors from occurring at both the testing laboratory and at the hospital.
If you are the first person in your family to get tested, a negative test result does not guarantee that you won't get cancer or that you don't have some other altered gene that could lead to cancer.
Without a known mutation in the family, a negative result for someone who has not had breast or ovarian cancer can mean several things:
1. Your family's cancer history was caused by a BRCA1 or BRCA2 alteration that you did not inherit; other family members could still be at risk
2. Your family's cancer history was caused by a different mutated gene, which you may or may not have inherited. (The test only identifies altered BRCA1 or BRCA2 genes — it does not test for every possible cancer-associated gene).
3. The cancer in your family was not caused by an inherited mutated gene, but may have a common environmental component (caused by exposure to some toxic substance, for example) or may have occurred by chance.
Your genetic counselor has no way of knowing which of these possibilities is the right one. A counselor can, however, assess the likelihood of each one of these options by examining your family history. This is why BRCA1/2 testing is only recommended for people whose family history suggests that they have a high chance of carrying an altered BRCA1 or BRCA2 gene.
It is also possible to get a "false negative" result. This means you may have an altered form of one of the genes, but the test did not detect it. Also, other genes besides BRCA1 and BRCA2 are involved in cancer risk. Your genetic counselor should be able to discuss this issue with you and give you a general idea of how likely a false negative result may be.
A variant result is a "maybe" answer. In some cases, the lab will eventually decide that the alteration is important and does increase the risk for cancer. In other cases, the lab may decide that the variant probably won't increase your risk for cancer. At the time that you get your test result, the lab may not know which one is the right answer. Your genetic counselor can try to help you sort through what a result like this means for you.