 Heredity and Breast Cancer—the BRCA Gene Breast Cancer Genetic Counseling Prophylactic Mastectomy for BRCA Gene Carriers Who Should be Tested for the BRCA Gene Mutations? Genetic Risk Factors for Breast Cancer Most Commonly Asked Questions1. How common are breast and ovarian cancer?Breast cancer is the most common type of cancer among American women, affecting about 1 in 8 during their lifetime. Ovarian cancer affects about 1 in 70 women. In 2001, about 180,000 individuals in the United States were diagnosed with breast cancer. As an individual ages, the chance of developing cancer increases. Breast cancer is uncommon in men, with male breast cancer accounting for less than 1% of all cases of breast cancer.2. How common is hereditary breast and ovarian cancer?It has been estimated that about 5 to 10 percent of all female breast and ovarian cancer cases are hereditary. The proportion of male breast cancer that is hereditary is thought to be similar. Hereditary cancers occur as the result of inheriting an alteration in a gene that increases the likelihood of developing breast or ovarian cancer. In most families with this inherited alteration in a gene, several individuals will be affected with cancer.3. How can an increased likelihood for breast cancer be inherited?Inherited information is contained in every cell in our body on structures called chromosomes. We have 46 chromosomes that come in 23 pairs; one member of each pair comes from our father, and the other from our mother. Each chromosome is made up of thousands of genes. Genes, like chromosomes, come in pairs. They are packages of genetic information (DNA) that act as instructions for making the substances that help our bodies to function properly. An alteration in this genetic information can interfere with proper body functions by causing the gene to no longer work. These gene alterations are called mutations.BRCA1 and BRCA2 are genes involved in cell growth, division, and repair of damage to DNA that occurs during ones lifetime when a spelling error is made in the genetic instructions. An altered (mutated) BRCA1 or BRCA2 gene increases the likelihood that cancer will develop. Individuals with mutations in either of these genes may be diagnosed with cancer at an earlier age and may develop breast cancer in both breasts (bilateral cancer). The most common types of cancers associated with BRCA1 and BRCA2 alterations are female breast and ovarian cancers. Having a BRCA2 mutation increases a man's chance of developing breast cancer. Men with BRCA1 mutations may also have an increased risk to develop breast cancer. It is important to remember that the majority of all breast cancers are not hereditary. Of those that are hereditary, about a third are due to mutations in the BRCA1 gene. About a third of the remaining hereditary breast cancers are due to mutations in the BRCA2 gene. There are additional, as yet unidentified breast cancer genes that account for the remaining hereditary breast cancer clusters. Other genes may account for the smaller fraction of families with both breast and ovarian cancer. 4. What are the chances of inheriting an altered BRCA1 or BRCA2 gene?Both of the BRCA genes, BRCA1 and BRCA2, are inherited in an autosomal dominant fashion. Autosomal means that both men and women can inherit and pass along a BRCA mutation. Dominant means that it only takes one altered breast cancer gene to cause the increased likelihood for developing cancer. All individuals, whether they have cancer or not, have two copies of both BRCA genes, one copy from each parent. If an individual has a parent with a BRCA1 or a BRCA2 mutation, he or she may either inherit that parent's altered (non-working) BRCA genes or the working BRCA genes. Therefore, that individual has a 50 percent chance of inheriting an altered BRCA gene and the increased likelihood to develop certain cancers. Likewise, the individual has a 50 percent chance of not inheriting an altered BRCA gene and would then have the same risk for developing cancer as a person in the general population.5. Are certain individuals more likely to have a particular gene mutation?Studies have shown that there are specific mutations of the BRCA1 and BRCA2 genes that are common in persons of Eastern European Jewish (Ashkenazi) origin. These mutations are called 185delAG and 6174delT. About 2 out of 100 individuals of Ashkenazi background have one of these mutations in their BRCA genes. Women of Ashkenazi backgrounds who have these mutations have an increased chance of developing breast and ovarian cancers. The same is true for other mutations of the BRCA genes. Our research indicates that about a quarter of women of Jewish background who are diagnosed with breast cancer before age 41 have one of these mutations.In addition to the 185delAG mutation of BRCA1 and the 6174delT mutation of BRCA2, there is another BRCA1 mutation called 5382insC that is also more common in those of Ashkenazi Jewish background. One in 40 Ashkenazi Jewish individuals have one of the three most common mutations of BRCA1 or BRCA2. Some families of Jewish origin with breast and ovarian cancer have been found to have mutations other than the three recurring ones, although mutations elsewhere are not as common. Certain BRCA mutations also appear more frequently in individuals from some Scandinavian countries, and other geographically isolated areas such as Iceland. 6. How are BRCA1 AND BRCA2 detected?It is possible to test for BRCA mutations. By taking a blood sample from someone who has had breast or ovarian cancer, the laboratory can detect alterations in these genes. Once an alteration has been found in a BRCA gene in someone with cancer, we can look for that same alteration in family members who have or have not had cancer. Presently, testing is not routinely available on material, such as stored tumors from deceased family members. Testing can also be performed on individuals without cancer even if there is no affected relative who wishes or is able to be tested. If a mutation is found, screening guidelines, described later in this document, would be recommended. However, the absence of a BRCA mutation in the unaffected person may be difficult to interpret. This is because the cancers in the family may have been due to different genes or other factors.7. What if testing does not detect a BRCA1 OR BRCA2 gene?Negative results (meaning a BRCA1 or BRCA2 mutation is not found) can mean several things. First, it might mean that there is a BRCA1 or BRCA2 gene mutation that cannot be detected by the testing method utilized. No one testing method will find all BRCA mutations. It could also mean that a different gene is responsible for the cancers in the family. Families who do not have a mutation in one of the genes may be interested in pursuing testing for other breast cancer genes in the future should other genetic tests become available. It is also possible that the cancers in the family are not hereditary. Since breast cancer is a common disease, by chance alone, more than one woman in a given family may have breast cancer. Finally, some individuals may participate in studies that only test for certain mutations (i.e. 185delAG) in the BRCA genes. If the particular mutation being tested for is not found in these individuals, there still may be a mutation in the BRCA genes for which he/she was not tested.8. What if testing reveals that an individual has inherited an altered BRCA1 gene?Women who inherit a BRCA1 mutation have an increased risk for developing breast and ovarian cancers. Research is taking place to determine the exact risks for developing these cancers. These risks may vary from family to family and from one individual to another. Women who have an altered BRCA1 gene have between a 50- 85 percent risk of developing breast cancer by age 70. Their risk for ovarian cancer ranges from 40-60 percent by age 85. A woman who has already had breast cancer and is found to have an altered BRCA1 gene has an increased risk for breast cancer in her other breast as well as for ovarian cancer. Recent studies suggest that up to 25-30 percent of women with a BRCA mutation may develop a contralateral or opposite breast cancer within ten years after an initial breast cancer diagnosis.In addition, men and women with a BRCA1 mutation may have an increased risk for developing colon cancer. Men with BRCA1 mutations also have an increased risk for developing prostate cancer, although the risk is not as high as for breast and ovarian cancer in women. During their lifetime, individuals who have inherited a BRCA1 mutation may develop one or more cancers, or none at all. It is not possible to predict ahead of time what type of cancer, if any, such a person will develop. 9. What if testing reveals an inherited BRCA2 mutation?Both men and women who inherit a BRCA2 mutation have an increased chance for developing breast cancer. Women who have an altered BRCA2 gene appear to have a similar risk of developing breast cancer compared to women with BRCA1 mutations. The risk for ovarian cancer is also increased. Studies suggest that the ovarian cancer risk is between 16 and 27 percent, respectively. The chance for a male with a BRCA2 mutation to develop breast cancer is quite low, but is considerably higher than the chance for male breast cancer in the general population. We do not have as much information about additional cancer risks with a BRCA2 mutation, although some studies suggest that colon, pancreatic, skin (melanoma), and prostate cancer risk may also be elevated. Further research is ongoing to better define the disease spectrum and these risks.10. What if I have a "variant" in a BRCA gene?Genes are written in letters called bases. There may be different spellings of bases in different people. Sometimes, a different spelling of bases can cause a disease. We are still learning which spellings are "normal" variants and which are "abnormal" and increase the risk for disease. If you have a "variant" BRCA gene we may not be able to tell you if this is a normal pattern. We may be able to test other family members, or do other lab tests to help learn if this variant increases your risk for cancer. However, there are times we cannot tell if a variant will increase your risk. If you have a variant we will advise you to follow breast and ovarian cancer screening recommendations.11. If a woman has an altered BRCA gene, what are the options?A woman with an altered BRCA gene has several options. The goal of these options is to prevent cancers or to find cancers at the earliest possible stage when they are most easily treated. Women with BRCA alterations should be sure to practice regular breast cancer screening. This means having yearly mammograms, having breast examinations by a physician at frequent intervals, and performing monthly breast self-examinations. Mammography screening and physician examination should start at least by age 25, and self-examination even earlier. Mammography does not detect all cancers at early stages. New screening approaches (breast ultrasound and/or breast MRI performed annually six months after the annual mammogram and/or more frequent mammography) are also being investigated.Screening for ovarian cancer is more difficult and current tests cannot always find early ovarian cancers. We generally recommend twice-a year ultrasound of the ovaries, pelvic examinations, and a blood test called CA125. The age at which to begin ultrasound screening remains unclear; however, we usually recommend beginning ultrasound screening starting around age 35. We now believe that the greatest risk for ovarian cancer in women with BRCA mutations is in the mid to late 40's; however, studies indicate that women with BRCA mutations remain at increased risk for ovarian cancer in their later years of life as well. Colon cancer screening is also recommended using colonoscopy on a regular basis starting at age 40-50. If there is no family history of colon cancer, a colonoscopy should be performed every 3 to 5 years. Another option is to take part in chemoprevention trials. These are experimental trials that use drugs in an attempt to prevent or delay the development of cancer. Examples are tamoxifen or raloxifene or other new agents that may prevent breast cancer. While tamoxifen has been shown to lower breast cancer risk in women with a family history of the disease, it is not clear whether and to what extent it is will be effective in preventing breast cancers among women with BRCA1 and BRCA2 mutations. Other studies suggest that oral contraceptives may reduce risk of hereditary ovarian cancer, although an increase in breast cancer risk has not been excluded. A third option is to have surgery to remove an at-risk organ before cancer develops. An example of this would be risk-reducing mastectomy, a type of surgery to remove the breasts in an attempt to prevent breast cancer. Women can also have their ovaries and fallopian tubes removed, a procedure known as "risk-reducing salpingo-oophorectomy," to decrease the chances of developing ovarian cancer. We do know that in rare cases, even these surgeries have not prevented breast, ovarian, or peritoneal cancers from occurring. For this reason, following risk-reducing removal of the ovaries, CA125 testing may still be considered due to the small risk of peritoneal cancer. Recent studies indicate that the earlier oophorectomy is performed, the greater the protection against both breast and ovarian cancer. We have observed cases of early-stage ovarian cancer (undetected by ultrasound) in women who have had risk-reducing ovarian surgery, which highlights the limitations of ovarian cancer screening. 12. If a man has an altered BRCA gene, what are the options?Because of the increased prostate cancer risk, prostate cancer screening is recommended for males with BRCA1 or BRCA2 mutations beginning between ages 40 and 50. Such screening consists of an annual digital rectal examination and serum prostate specific antigen (PSA) screening.We advise the use of colonoscopy to screen for colon cancer every 3 to 5 years beginning between ages 40 and 50. 13. If a person doesn't want genetic testing, what are the options?It is possible to assess a person's familial cancer risk without genetic testing. Testing may sometimes, but not always, improve the estimate of that risk. If a person does not have testing, but does have a close relative or multiple relatives who had breast cancer at an early age, or ovarian cancer at any age, it is important to start screening for both of these cancers. Screening for breast cancer involves yearly mammograms, physician examinations and monthly self-examination. Ovarian screening consists of physician exam, transvaginal ultrasound, and CA125 blood tests.14. What are the possible risk and benefits of BRCA1 and BRCA2 testing?The following risks and benefits should be considered before undergoing testing. There is no physical risk from testing other than that of a routine blood draw. The process of genetic testing may be emotionally difficult regardless of whether a BRCA1 or BRCA2 mutation is found. Once an alteration is found, this result may indirectly provide information about other family members, who may have chosen not to be tested. In addition, health care costs for the cancer screening and prevention options may or may not be covered by health insurance.Another issue of genetic testing is the possibility that the results could be used by an employer or insurance company to discriminate against an individual. Insurers may seek higher health insurance rates, cancel or deny policies for individuals with genetic "pre-existing conditions". Several states have outlawed "genetic discrimination" by insurers but no such law currently exists in New York. State laws may not apply to some businesses that provide their own health insurance. At present, however, we are not aware of any instances of genetic discrimination against any individuals who have received breast and ovarian cancer genetic testing as part of research studies at Memorial Hospital. Some insurers have begun to cover costs of genetic testing. The possible advantages of learning BRCA1 and BRCA2 test results include: reduced uncertainty about cancer risk, the ability to appropriately increase or decrease cancer screening depending on the results of testing, and consider other options for cancer risk-reduction. 15. How is the confidentiality of genetic testing information protected?In New York State, by law, the results of a person's genetic test can be given to no one without that person's written permission. At Memorial, testing is generally offered as part of research studies. For this reason, test results are stored in a file separate from the regular medical record. In many cases, we have obtained certificates of confidentiality from federal agencies to protect research information in these files. Should you verbally communicate test information to anyone else, that information may be recorded in your medical record. Should a person desire counseling for cancer risk based only on family history, that information will be part of the medical record.16. Will insurance cover genetic counseling and testing?We have successfully recovered costs for genetic counseling for cancer risk from many insurance plans. Because of special concerns about confidentiality of genetic testing, many individuals have chosen to pay directly for testing. Increasingly, however, some insurers and managed care providers are covering costs of genetic testing for cancer risk. Individuals may want to learn more about the policies of their health care provider prior to submitting charges for genetic testing.17. Should I be tested?The decision to participate in BRCA1 or BRCA2 testing is a complicated one. Individuals and families must not only weigh the risks and benefits of testing, they must also consider their unique situations. Ultimately, individuals must make their own decisions. These are best made after discussion with genetic counselors, physicians, and other health care professionals experienced in this area.Credit for Article Prophylactic Mastectomy for BRCA Gene CarriersA new Mayo Clinic study indicates that prophylactic removal of both breasts reduces the risk of a subsequent breast cancer by 89.5 – 100 percent in women known to be carriers of mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes — and thus at extremely high risk for developing the disease. The study, published in the Journal of the National Cancer Institute, followed 26 high-risk women with altered BRCA1 and BRCA2 breast cancer susceptibility genes. All of the women had previously undergone surgery to have their breasts removed. During the follow-up period — averaging 13.4 years — none of the women developed breast cancer. “Calculations predict that six to nine breast cancers should have developed in this group of carriers without prophylactic surgery,” said Dr. Lynn Hartmann, the lead investigator on the study. “That translates into a risk reduction of 89.5 percent to 100 percent for bilateral prophylactic mastectomy.” An earlier Mayo Clinic study followed 214 women with a strong family history of breast cancer who had previously had prophylactic mastectomy. Women in this surgical group were compared with their sisters who had not had prophylactic mastectomy. That study showed that prophylactic mastectomy reduced the risk of subsequent breast cancer by approximately 90 percent for high-risk women. For this new study, Hartmann’s team determined the BRCA1 and BRCA2 status of these original 214 high-risk women. Blood samples were obtained from 176 of the 214 women. Twenty-six of these women were identified to have altered BRCA1 and BRCA2 genes and they formed the study group for the new study. “Our previous study had shown that prophylactic mastectomy reduced subsequent breast cancer risk substantially in women who had the procedure because of a strong family history,” said Hartmann. “But a question remained: Would the procedure be able to reduce risk in the highest risk group — namely BRCA1 and BRCA2 carriers?” Hartmann said that this new study supported the conclusion that prophylactic mastectomy did have a significant preventive benefit in women with the BRCA1 and BRCA2 genetic mutations. She added that even though the number of women in the study (26) was small, a similar study by Dutch researchers on a larger group of women demonstrated the same benefit. Credit for Article |
