About 5 to 10 percent of people diagnosed with breast cancer have inherited an increased risk of developing the disease. In these cases, breast cancer runs in the family. Similarly, 5 to 10 percent of ovarian cancers diagnosed are hereditary.
BRCA1 and BRCA2 Genes
The genes BRCA1 and BRCA2 are involved in cell growth, cell division, and the repair of damage to DNA. Mutations in the BRCA genes can cause DNA damage in cells to go unrepaired, which increases the chance that a person will develop some types of cancer.
Breast and ovarian cancer are the most common diseases linked to BRCA1 and BRCA2 changes, but mutated forms of the BRCA genes may increase people’s risk for other cancers as well. For example, men with BRCA2 mutations are at increased risk of getting prostate cancer.
In general, people with BRCA mutations have an increased risk of getting cancer at an early age, developing breast cancer in both breasts, or developing more than one type of cancer in their lifetime. For people with no personal or family history of breast or ovarian cancer, the likelihood of carrying a BRCA mutation is very low.
In addition to BRCA1 and BRCA2, there are other gene mutations that can cause breast or ovarian cancer to run in a family, some of which have not yet been identified.
All people have two copies of the genes BRCA1 and BRCA2, and both men and women can pass down mutations in these genes.
If you have a parent with a BRCA1 or BRCA2 mutation, there is a chance you inherited either the mutated (nonworking) BRCA gene or the working BRCA gene from this parent.
You have a 50 percent chance of having inherited the nonworking BRCA gene, which would cause you to have an increased risk for cancer. There is also a 50 percent chance that you have inherited a working BRCA gene, in which case you have the same risk for cancer as a person in the general population.
Mutations of the BRCA genes have been found in people all over the world. However, these gene changes are more common in some groups, including Eastern European Jews, known as Ashkenazi Jews, and people from Iceland, Denmark, and French Canada.
Three BRCA mutations – called 185delAG, 6174delT, and 5382insC – are particularly common among Ashkenazi Jewish families, with one in 40 people carrying at least one of the mutations.
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 mentioned here, though such BRCA changes do not occur frequently.
Our researchers have conducted a review of cancer incidence in 165 families with three or more breast cancer cases but no BRCA1 or BRCA2 mutations. The study showed an increased risk for breast cancer among women in these families, but no increased risk for ovarian cancer. The findings support our hypothesis that most ovarian cancer occurring with breast cancer in the same family is linked to BRCA1 and BRCA2.
On average, women with an altered BRCA1 gene have a 50 to 85 percent risk of developing breast cancer by age 70. Their risk of developing ovarian cancer 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 mutation may get a second breast cancer within ten years after their first incidence of breast cancer.
In both men and women, BRCA1 changes also increase the risk for certain other cancers. People with a BRCA1 mutation may get one or more cancers, or never be diagnosed with cancer.
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 — a 50 to 85 percent risk of developing the disease by the age of 70. The risk for cancer of the ovary is also increased — between 16 and 27 percent by late age.
DNA is made up of four chemical bases – called A, T, C, and G – that are strung together in a specific order. In many genes, the sequence or order of bases may differ between people. Such variations are often harmless, but there are cases when the misspelling, or wrong order, of individual bases can cause a disease. We are still learning which spellings are “normal” or harmless variants.
If you have what is called a variant of uncertain significance in one of your BRCA genes, we may do lab tests to learn if the variant changes your cancer risk. However, 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, and we may also be able to test your relatives for this variant.
Genetic Testing for Hereditary Breast and Ovarian Cancer
A number of tests are available to find out if a person has inherited a mutation in BRCA1 or BRCA2.
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.
If a DNA change is found, other family members may be tested for that same mutation only. 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 one of several things:
- There is a BRCA1 or BRCA2 mutation that cannot be detected by the testing method used. There is no test that can find all BRCA mutations.
- 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.
- 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 probably has the same risk for BRCA-related cancers as the general population.
- Genetic testing does not always identify genetic mutations, even when your family history suggests that an inherited predisposition to cancer is likely. In the past, genetic testing could not identify large missing or rearranged portions of BRCA1 or BRCA2 genes that are known to play a role in the development of hereditary breast and ovarian cancers.
In 2002, a test that could identify five large changes in the BRCA1 gene was developed and has since been included in the full-sequence testing of BRCA. In September 2006, another test that can identify additional large changes in both the BRCA1 and BRCA2 genes became available. The latter test is not currently used for routine BRCA1 and BRCA2 genetic testing, although this may change.
If you received genetic testing for mutations in the BRCA1 and BRCA2 genes at Memorial Sloan Kettering prior to September 2006, and the results were negative or uninformative (no mutation or an “uncertain variant” was identified), you may benefit from learning more about the new testing. However, this testing is not applicable for individuals who have tested negative for a specific mutation already known to be present in their family.
For families with multiple cases of breast or ovarian cancer but no known BRCA mutations, testing for additional cancer-causing mutations – including changes in the genes CHEK2 and PALB2 – may be available. Such genetic testing is typically performed by testing a panel of genes at the same time.
Studies are currently under way to discover additional heritable gene mutations that may increase a person’s risk for breast and ovarian cancer.
Screening for Hereditary Breast and Ovarian Cancers
The goal of screening is to prevent cancer or to find the disease at an early stage, increasing the chance that it can be treated.
It is strongly recommended that women with BRCA changes are screened for breast cancer regularly. There are many types of screening, including mammograms, MRI exams, ultrasound, breast exams performed by a physician, and monthly breast self-exams.
Memorial Sloan Kettering provides breast and ovarian cancer screening guidelines for women based on their risk level.
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.
If there is a history of cancer in your family, we recommend you have regular screening, regardless of whether you have received genetic testing.
Reducing Your Risk of Developing Hereditary Breast or Ovarian Cancer
Women with BRCA mutations may wish to consider taking drugs that prevent or delay cancer onset to help reduce their cancer risk. Examples include tamoxifen and raloxifene, which can lower breast cancer risk in the general population. However, it is not clear whether these drugs reduce breast cancer risk in women with BRCA1 and BRCA2 changes.
Oral contraceptives may be taken to reduce the risk of ovarian cancer. However, it remains uncertain whether oral contraceptives have an impact on breast cancer risk in BRCA mutation carriers.
Women with BRCA mutations may choose to have surgery to reduce their cancer risk. For example, the breasts may be removed to prevent breast cancer, and the ovaries and fallopian tubes may be removed to prevent ovarian cancer. 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 breast and ovarian cancer. 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 peritoneal cancer risk, but we are currently conducting a study to see if CA125 blood tests after surgery can detect cancer of the peritoneum.