Breast/Ovarian Cancer: BRCA1 & BRCA2

Breast cancer is the most common cancer of women in the US, affecting about one in eight during their lifetime. Ovarian cancer is less common, affecting about one in 70 women. Breast cancer affects men, but it is uncommon, accounting for less than 1 percent of all breast cancer cases. In 2007, about 200,000 women and 1,600 men in the US had breast cancer. As a person ages, the chance of getting breast cancer increases. 

About 5 to 10 percent of breast cancers are hereditary. In these cases, breast cancer runs in the family. Similarly, 5 to 10 percent of ovarian cancer is hereditary. Hereditary cancer occurs because of a change in genes that is passed down to children. Some genetic changes cause an increased risk of cancer. In families passing an inherited change in a gene, multiple family members get the same type of cancer.

BRCA1 and BRCA2 are genes involved in cell growth, cell division, and repair of damage to DNA. DNA damage occurs when a spelling error is made in the gene sequence. A changed BRCA gene can cause DNA damage in cells to go unrepaired, which increases the chance that cancer will occur. People with BRCA mutations thus may get cancer at an early age, they may develop breast cancer in both breasts, or they may develop more than one type of cancer, e.g., cancers of both the breast and the ovary. The most common type of cancer linked to BRCA1 and BRCA2 changes is breast cancer, but mutated forms of BRCA genes are linked to other cancers as well. For example, men with BRCA2 mutations are at increased risk of getting prostate cancer.

Most breast cancers are not due to inherited changes in genes. Of those that are, about a third are due to mutations in the BRCA1 gene. Another third of breast cancers that run in families are linked to mutations in the BRCA2 gene. There are other gene mutations that can cause breast cancer to run in a family. We have not found all of these genes.

Both men and women can pass down a BRCA mutation. All people, whether they have cancer or not, have two copies of both BRCA genes -- one copy from each parent. If you have a parent with a BRCA1 or BRCA2 mutation, you may inherit that parent's mutated (nonworking) BRCA gene, or you may inherit the working BRCA gene. In other words, you have a 50 percent chance of inheriting either copy of each parent's two BRCA genes. If you inherit a nonworking BRCA gene, you will have an increased risk for cancer. Even though you may inherit a working BRCA copy from the other parent, it takes only one altered BRCA gene to increase risk for breast or ovarian cancer. You also have a 50 percent chance of not inheriting a nonworking BRCA gene from a parent who carries a mutation. If that is the case you have the same risk for cancer as a person in the general population. 

Mutations of the BRCA genes are more common in some groups. One such group is Eastern European Jews, who are known as Ashkenazi Jews. In Ashkenazi Jews, three BRCA  mutations in particular are more common, with one in 40 people carrying one of these common BRCA mutations. 

The most common BRCA changes among Ashkenazi Jews are called 185delAG, 6174delT, and 5382insC. Women with these mutations have a greater risk of developing cancer of the breast and ovary. About 25 percent of Jewish women who have developed breast cancer by age 41 have one of these BRCA mutations. People of Ashkenazi Jewish descent can have BRCA changes other than the common ones listed here, though such BRCA changes do not occur frequently.

Certain BRCA changes are also more common in other groups. These groups include people from Iceland, Denmark, and French Canada.

For patients who have no personal or family history of breast or ovarian cancer, the likelihood of carrying a BRCA mutation is very low.

By analyzing a blood or saliva sample, a lab can detect DNA changes that indicate a mutation in one of these two genes. If more than one family member is interested in being tested, it is best to start BRCA testing with a person who has (or had) cancer of the breast or ovary. Once a DNA change has been found, that same mutation can be tested for in other family members. Testing for BRCA mutations on stored samples of DNA from deceased relatives is also possible.

Negative results (meaning no BRCA1 or BRCA2 change is found) can indicate several things:

• First, it might mean that there is a BRCA1 or BRCA2 mutation that cannot be detected by the testing method used. No one testing method can find all BRCA mutations.



• A negative test also could mean that a gene other than BRCA caused the cancers that occurred in the family. At present, tests for genes other than BRCA are only conducted in special cases.



• It is also possible that any breast or ovarian cancers in the family occurred simply by chance. Since breast cancer is common, more than one woman in a given family may develop breast cancer for reasons unrelated to heredity.



• Sometimes an individual may opt to test only for a certain mutation (for example, 185delAG) in the BRCA genes. If the mutation is not found, there still may be a mutation in the BRCA genes for which the individual was not tested.



• Finally, if someone with a known BRCA mutation in his or her family is tested and receives a negative result, the individual does not have that BRCA mutation. He or she has the same cancer risk as the general population.

Women with a mutation in the BRCA1 gene are at increased risk for cancer of the breast and ovary. These risks may vary. Women with an altered BRCA1 gene have a 50 to 85 percent risk of developing breast cancer by age 70. Risk for cancer of the ovary is 40 to 60 percent by age 85. 

A woman with cancer in one breast has a higher risk of developing cancer in the other breast. Twenty-five to 30 percent of those with a BRCA1 change may get a second breast cancer within ten years after their first incidence of breast cancer.

Men and women with a BRCA1 change have an increased risk for certain other cancers. Those with a BRCA1 mutation may get one or more cancers, or none at all. 

Both men and women with a change in the BRCA2 gene are at increased risk for breast cancer. In women, the risks associated with a BRCA2 mutation appear to be about the same as those for BRCA1 mutations. The risk for cancer of the ovary is also increased — between 16 and 27 percent by late age.

A male with a BRCA2 change has an increased risk for breast cancer. Men with BRCA2 hanges also have a higher risk of prostate cancer. The risk for pancreas cancer and melanoma also are increased in individuals with BRCA2 changes.

The names of genes consist of a string of letters, each of which represents a chemical base and the order in which it appears on the gene. The sequence, or order, of bases may differ in people. If the bases appear in the wrong order, or are misspelled, this can cause a disease. We are still learning which spellings are "normal" variants. If you have what is called a variant BRCA gene we may not be able to tell you if this is a normal pattern. We may do lab tests to learn if the variant changes cancer risk. There are times when we cannot tell if a variant will increase your risk. If you have a variant, we will make recommendations for cancer screening based on your family history. We may also be able to test relatives for this variant.

A woman with an altered BRCA gene has several options for cancer screening, the goal being to a) prevent cancer and b) find the cancer at an early enough stage that it can be treated. Women with BRCA changes should be sure to employ breast cancer screening, of which there are many different types. These include mammograms, MRI exams, ultrasound, breast exams performed by a physician, and monthly breast self-exams. Women with altered BRCA genes who are age 25 and older should receive regular mammograms and begin conducting self-exams by age 18. MRI scans may also be recommended as this test can find breast cancers not detected by mammograms or ultrasound. The ideal way to combine these three tests is still being defined. Mammograms and MRIs may either be done at the same time or spaced six months apart. Some experts are concerned about risks of mammograms in very young women. We do not yet know if the risks undermine the known benefits of early screening for this group. For more information about MRI exams, see Clinical Research Updates.

Screening for ovarian cancer has not proven to be beneficial. We suggest ultrasound of the ovaries, a pelvic exam, and a blood test called CA125 twice a year. Although the age at which regular ultrasound screening should begin is not clear, for women with a BRCA1 mutation we suggest beginning ultrasound screening between ages 30 and 35. For women with BRCA2 mutations, screening should start between ages 35 and 40. Women with BRCA changes are at increased risk for ovarian cancer later in life as well.

Colon cancer screening should start by age 50 for the general population. Colonoscopy is the best method to screen for the disease. Your doctor will make a recommendation of when and how often to screen, but generally it should take place every five to ten years.

Another option women with BRCA mutations may wish to consider is drugs that decrease cancer risk by preventing or delaying cancer onset. Examples include tamoxifen and raloxifene, which can lower breast cancer risk in the general population. It is not clear whether they reduce breast cancer risk in women with BRCA1 and BRCA2 changes. Oral contraceptives may also be taken to reduce the risk of ovarian cancer. However, oral contraceptives may increase breast cancer risk in those with BRCA changes.

Surgery may be advisable to reduce cancer risk for some women with BRCA mutations. For example, breast tissue may be removed to prevent breast cancer, and removal of the ovaries and fallopian tubes decreases the chances of cancer of the ovary. Removing the fallopian tubes and ovaries before age 50 also reduces breast cancer risk.

Other surgeries may be performed to help detect cancers early. The earlier the ovaries are removed, the greater the decrease in risk for both cancer of the breast and ovary. In rare cases, a cancer of the peritoneum, which lines the wall of the abdomen, may develop after such surgery. There is no proven way to screen for the risk of peritoneal cancer. We are currently conducting a study to see if CA125 blood tests after surgery can detect cancer of the peritoneum.

Men with BRCA mutations should receive regular prostate cancer screenings. The age to start screening is not yet clear, but prostate cancers do not seem to occur early in men with BRCA changes. As a precaution, we recommend that screening for prostate cancer begin by age 40, though age 50 may also be adequate. Screening consists of a yearly exam by a doctor and a blood test known as a PSA test.

There is an increased risk of breast cancer among men with BRCA changes. Men who carry a mutated BRCA should have regular exams and mammography if possible in addition to having breast masses evaluated.

Colon screening should begin by age 50. We advise colonoscopy every five to ten years.

Cancer risk can be evaluated even without genetic testing. This can be done by looking at family history, and in some cases genetic testing may not improve the risk estimate. Anyone with a family history of cancer should be regularly screened (see options above) regardless of whether he or she has received genetic testing. Screening for breast cancer includes mammograms, MRI exams, exams performed by a physician, and self-exams. Screening for ovarian cancer, while less effective, consists of pelvic exams, ultrasound, and CA125 blood tests. In some cases, surgery for prevention of cancer may be done even without genetic testing.

Anyone considering genetic testing should be aware of the possible benefits and risks. There are four possible benefits to testing for BRCA1 and BRCA2 mutations. First, the results may provide a better measure of your cancer risk. Second, the results allow you to tailor cancer screening as needed. Third, the results can guide you in choosing options for cancer-risk reduction, such as surgery. Finally, knowing the test results may benefit others in your family.

While genetic testing poses no physical risk other than that of a blood draw, it may have an emotional impact. This is of special concern if a BRCA1 or BRCA2 change is found and may also have an impact on family members, some of whom may not want to know the results.

Another risk associated with genetic testing is that there is a chance that someone could use the results against you. This is a form of discrimination. Federal and state laws are in place to prevent the use of genetic tests results in this way. For example, employers cannot use the results as a reason to fire you or to refuse to give you a job. In addition, insurance providers cannot use genetic test results to deny you health insurance, nor can they use test results to raise the cost of your current health insurance. Despite these safeguards, we cannot fully guarantee you that no one will ever use the results of a genetic test against you.

We do not know of anyone who has experienced insurance or work problems after having had genetic testing at Memorial Sloan-Kettering. Most insurers now cover costs of genetic testing with no penalty, though this has not always been the case.

Your entire medical record, including your genetic test results, is kept private and in confidence. Only two types of people have access to your medical records. The first are people who run the tests. The second are those who provide your medical care. If you would like to know more about our Center's privacy policy, please let us know. If you would like a copy of our privacy notice, we would be happy to assist you.

We have received payment from many insurance and managed care plans, both for genetic testing and for counseling. Some patients choose to pay for genetic testing themselves. You may want to learn more from your healthcare provider prior to having the test done and submitting charges for the testing.

The decision to have BRCA1 or BRCA2 testing is a personal one. A decision is best made after discussion with a genetic counselor. Physicians and other healthcare professionals may also help you decide whether or not to undergo genetic testing. But in the end, the decision to have genetic testing is yours, once you have weighed the possible risks and benefits.