30 May 2013

Genetic testing for BRCA1 & BRCA2 mutations

Whether you and/or some of your family members have had breast cancer, you may be interested in the possibility of genetic testing. The best way to get started is to learn more about your family history on both your mother’s and your father’s side. A BRCA mutation is more likely to run in your family if:

• Many women in your family have had breast and/or ovarian cancer, particularly at a younger age than these cancers typically develop (before age 50).
• Some women in your family have had cancer involving both breasts.
• There is both breast and ovarian cancer in your family.
• Men in your family have had breast cancer.
• There is breast cancer in your family and either male relatives on the same side of the family have had prostate cancer at a young age, or male or female relatives on the same side of the family have had gastrointestinal cancers, such as cancer of the pancreas, gall bladder, or stomach.
• Your family is of Ashkenazi (Eastern European) Jewish descent.

If any of these are true for either side of your family, you may be a candidate for genetic testing. You may want to meet with a genetic counselor, a medical professional specially trained to understand and provide information about genetics and disease

Your genetic counselor will help you figure out if your family history suggests an inherited pattern to the cases of breast cancer — and perhaps ovarian and other types of cancer — that have occurred. If so, a BRCA1 or BRCA2 mutation may be causing the cancer in your family. The only way to know for sure is to undergo genetic testing.

Genetic testing results are most meaningful when the process begins with a family member who has already been diagnosed with breast cancer or ovarian cancer. That may be you, or it may be your mother, aunt, sister, or another family member. Here’s why:

• Even if a BRCA mutation is present in your family, not every person in the family will have inherited it. It’s more likely that someone who has had breast or ovarian cancer will have the mutation. Once you verify that a relative with cancer has the BRCA1 or BRCA2 mutation, then it’s very likely that the cancers in your family are being caused by the mutation. Family members who then test positive should  consider themselves to be at high risk of developing breast or ovarian cancer. Those who test negative can view their risk as similar to that of people in the general population.
• If a family member with breast or ovarian cancer tests negative for the BRCA mutations, then it’s possible that a strong pattern of cancer in      your family is due to some other inherited gene yet to be discovered by researchers. Based on family history alone, you and your relatives still should consider your risk of breast  and ovarian cancer to be higher than that of the general population.

Sometimes, there are no living relatives with cancer who can undergo genetic testing. A genetic counselor can help you decide who in the family is the best person to test and why.

Genetic testing for breast cancer risk can have a major impact on people’s lives. Before you or your relatives get tested, you must sign an informed consent document, which states that you have been fully informed of the benefits and risks of testing. Your genetic counselor likely will discuss the benefits and risks with you and give you some information to read on your own.

The main benefit of testing is knowledge. If you know that the breast and ovarian cancer in your family is due to a genetic mutation and you test negative, this means you are not at high risk due to a BRCA gene abnormality. But depending on other factors, including a close family member who had breast cancer that was not related to BRCA1 or 2 mutations, you could still be at high risk due to some other inherited gene yet to be discovered. If you test positive, you can take steps to prevent these cancers, or try to catch them early if they do develop.

Making decisions about genetic testing is a process that takes time and thought, and you may need a few sessions with your genetic counselor before you can make up your mind.

After you receive your test results, it is important to have a genetic counselor or other qualified healthcare professional interpret the results and discuss your health management options with you. This will make it easier for you to talk with your other doctors, who will help you make decisions about how best to address your cancer risks.

If you’re thinking about learning whether you have mutations for the BRCA1 or 2 genes, it’s important consider both the benefits and drawbacks of learning this information.

Here are the advantages of seeking genetic testing:

If you have a family member with a confirmed BRCA mutation, and your test result is negative, your genetic counselor can tell you with greater certainty that you have the same relatively low risk of developing breast or ovarian cancer as people in the general population. Routine screening for breast cancer (self-exams, mammograms,doctor visits) will still be important for you, just as it is for all women. For ovarian cancer there are currently no widely accepted screening guidelines for women at average risk of developing the disease. Men with a negative test result know that they have the same extremely low risk of getting male breast cancer as men in the general population, and the same relatively low risk of prostate cancer.

If your test result is positive, there are steps you can take to lower your risk of breast and/or ovarian cancer, or try to detect these cancers early if they should ever develop:

• Talk to your doctor about the possibility of taking a medication  such as tamoxifen, which could reduce your risk of developing breast cancer, or oral contraceptives, which could reduce your risk of ovarian cancer. While data is not clear on the safety of oral contraceptives in people at high risk for breast cancer, some doctors do recommend them for carriers of BRCA1 and BRCA2 mutations. This recommendation depends on factors including which mutation you carry and how much breast or ovarian cancer is in your family. Weigh the pros and cons of oral contraceptives with your doctor.
• You might take advantage of more frequent clinical exams and breast screenings — every 6 months instead of once per year — and ask for digital  mammography (versus film screen mammography) and/or MRI (magnetic resonance imaging) in addition to mammography. You also may wish to have regular pelvic exams and ultrasounds, and possibly a blood test called CA-125, in an attempt to detect any early signs of ovarian cancer.
• You may consider preventive (prophylactic) surgical removal of your breasts, ovaries, or both before cancer has an opportunity to form.
• If you do develop cancer, you and your doctor will be able to make treatment decisions that take your genetic information into account.
• Knowing that you carry a BRCA mutation may prompt you and your family members to make lifestyle and family planning changes or other decisions that could help lower cancer risk.

Men who test positive for BRCA mutations are considered to be at higher-than-average risk for prostate cancer. They can talk with their doctors about beginning screenings, including an annual digital rectal examination and PSA (prostate-specific antigen) blood test between ages 40 and 50. Their risk of male breast cancer is still relatively low, but higher than it is for men who do not have the mutation. Men should be sure to report any unusual breast changes or lumps to their doctors immediately.

Genetic testing also has limitations and possible drawbacks, including the following:

• It’s not yet clear exactly what you should or shouldn’t do once you get your genetic test results. We still don’t know the most effective ways to prevent breast or ovarian cancer, although taking certain medications,  such as tamoxifen for breast cancer and, in some cases, oral contraceptives for ovarian cancer, could lower your risk of developing these diseases.
• Removing the breasts and ovaries to lower cancer risk (called prophylactic surgery) does not get rid of every breast- and ovary-related cell. So even though surgery lowers your risk dramatically, it still does not entirely eliminate the risk. Even after such surgery, a woman with an abnormal breast cancer gene must be monitored regularly. These diseases may show up in nearby tissues and organs.
• Normal test results don’t guarantee healthy genes. In some families, many women have had breast cancer, yet they all test normal for the known breast cancer mutations. These families may have an inherited form of breast cancer caused by an abnormality or other gene that simply  hasn’t been identified yet. Also, if a woman tests negative for the mutations but the presence of a mutation has not been confirmed in a family member with cancer, she still is considered high-risk. In these situations, women need to be followed closely by their doctors.
• Close monitoring with regular exams and screening does not always succeed in detecting breast and/or ovarian cancer early. Some women end up being diagnosed with later-stage disease despite the best surveillance techniques.
• For some women, an abnormal test result can trigger anxiety, depression, or anger. Even though the result doesn’t mean that a woman will definitely get breast cancer, many women with an abnormal gene assume they will. If you think knowing the information may be too hard for you emotionally, you might consider not having genetic testing until more is known about how to prevent and treat the disease.
• If you learn that you’ve passed on an abnormal gene to your  children, you may feel guilty and worried. (Yet such knowledge may also prepare you for helping your children cope with their genetic information.)
• Genetic testing may not answer all your questions. In families with an abnormal breast cancer gene, other factors that are not yet understood may contribute to high risk