BRCA1 & BRCA2: Genetic testing for hereditary breast and ovarian cancer patient guide

BRCA1 & BRCA2: Genetic testing for hereditary breast and ovarian cancer patient guide

What is Hereditary? Breast cancer is the most common cancer in women in the U.S. (it affects about 1 in 8 women). Ovarian cancer affects about 1 in 71 women. The majority of breast and ovarian cancer cases occur at older ages in people with little or no family history of the disease and no genetic risk. These occurrences are called sporadic cancers and happen by chance. Although many people have a family history of cancer, the majority of breast and ovarian cancers are not due to inherited causes. Only about 10% of cancer is hereditary (due to inherited genetic changes called mutations). People who carry these mutations are born with them they do not develop over time. Understanding if cancer is due to an inherited mutation can help clarify future risks to develop cancer and help determine options for cancer screening and prevention. cancer type breakdown breast cancer Sporadic 70-80% Familial, 15-20% Hereditary, 5-10% BRCA1 and BRCA2 are the most common causes of hereditary breast and hereditary ovarian cancer ovarian cancer Sporadic 75-90% Hereditary, 10-25% BRCA1 and BRCA2 cause 50-75% of inherited ovarian cancers Many families with a history of breast and/or ovarian cancer do not have an identifiable genetic cause. These familial cases may be due to other genes, shared factors such as environment and lifestyle, or a combination of all of these. notes

What is Your Risk for Breast and/or Ovarian? Risk assessment by a healthcare provider can help define your chance of developing breast and ovarian cancer. A woman with no family history of breast or ovarian cancer is most likely at average risk (shown on the graph below as general population risk). For a person who has a family history of breast and/or ovarian cancer, BRCA1/2 genetic testing may be appropriate to help determine his/her risk of developing breast or ovarian cancer. If someone has had breast or ovarian cancer, BRCA1/2 genetic testing may be appropriate to help determine if she/he has an increased risk for additional cancers. Defining a person s cancer risk helps his/her healthcare providers make personalized recommendations for cancer screening and prevention. What are the BRCA1 and BRCA2 Genes? Everyone has two copies of the BRCA1 and BRCA2 genes, which we randomly inherit from each of our parents. Their function is to help prevent cancer in specific body parts. If the BRCA1 or BRCA2 gene is not functioning properly (due to an inherited gene mutation), then there is an increased risk for breast, ovarian, pancreatic, prostate, and male breast cancer. brca1/2 lifetime cancer risks (%) 45-87 General Population BRCA1/2 Positive 11-40 15-20 12 2 0.1 5-10 14 Breast Ovarian Male Breast Prostate BRCA1/2 mutation carriers often develop cancer at younger than typical ages and have an increased risk for second primary tumors to develop additional cancers in the same or different organ. This genetic test analyzes the BRCA1 and BRCA2 genes to identify any inherited changes (mutations) in them that increase the risk for cancer.

Is BRCA1 and BRCA2 Genetic Testing Appropriate for You? Genetic testing may be appropriate if you have a personal history and/or family history of any of the following: Breast cancer diagnosed at age 45 or younger Triple negative* breast cancer diagnosed age 60 or younger Bilateral breast cancer (breast cancer in both breasts) Ovarian, fallopian tube, or primary peritoneal cancer at any age Ashkenazi Jewish ancestry with breast cancer at any age Male breast cancer at any age Three or more cases of breast, ovarian, pancreatic, and/or prostate cancer (on the same side of the family) Known BRCA1 or BRCA2 mutation in the family * Triple negative refers to breast cancers that are estrogen receptor, progesterone receptor, and HER2/neu negative. This is determined by the pathology reports related to your cancer. Genetic Test Results Explained A patient undergoing genetic testing will receive one of three possible results: positive, negative, or inconclusive (i.e. variant of unknown significance or VUS). RESULTS Positive Negative Inconclusive EXPLANATION A mutation was found in one of the genes tested Increased risk for cancer specific to the gene that has a mutation Gene-specific cancer screening and prevention recommendations Offering genetic testing to adult at-risk relatives for the specific mutation is recommended No changes, or mutations, were found in any of the genes tested risk(s) are based on personal and family history screening and prevention recommendations based on family history Genetic testing most likely will not be appropriate for family members A genetic change was found, but it is unclear if this change causes an increased risk for cancer or not risk(s) are specific to the family history of cancer screening and prevention recommendations based on family history Family research studies may be helpful There is a 50/50 random chance to pass on a genetic mutation in BRCA1 or BRCA2 to your sons and daughters. The image to the right shows that both men and women can carry and pass on these mutations. Has genetic mutation No mutation

Medical Recommendations for Patients With a BRCA1/2 Mutation WOMEN Breast Management Ovarian Management Breast awareness starting at 18 Clinical breast exam every 6-12 months and breast MRI annually, starting at age 25 Annual breast MRI and mammogram at age 30-75 Optional risk-reducing mastectomy (surgery to remove breasts) Discuss options for medications that may reduce risk, such as tamoxifen Risk-reducing surgery to remove ovaries and fallopian tubes (salpingo oophorectomy) between age 35-40 or after completion of childbearing Consider transvaginal ultrasound and a blood test called CA-125 every 6 months beginning at age 30 or 5-10 years before the earliest ovarian cancer in the family Discuss options for medications that may reduce risk, such as birth control pills MEN Breast Management Prostate Management Breast self-exam training and education starting at age 35 Clinical breast exam every 6-12 months starting at age 35 Consider mammogram at age 40; annual mammogram if indicated based on baseline study findings Consider prostate screening starting at age 40 with digital rectal exam and PSA Medical Recommendations for Patients with No Mutation Detected For patients with a personal history of breast cancer, stage appropriate care and follow-up are recommended. For patients with a family history of ovarian cancer (no personal history): Discuss ovarian cancer screening and the possibility of a preventive surgery with your physician For patients with a family history of breast cancer (no personal history): Discuss breast cancer screening and the possibility of a preventive surgery with your physician If there is a known BRCA1/2 mutation in the family and you test negative, general breast cancer screening is most likely appropriate. If there are other types of cancers in the family, other screening and prevention options may be appropriate, and should be specific to cancers in the family.

Common Questions About Genetic Testing q1. will genetic testing be covered by my insurance? When patients have a personal or family history of cancer similar to what is described on page 2, genetic testing is typically covered, and most patients have coverage at 90 or 100%. Ambry Genetics works closely with insurance companies through a coverage verification process. If out-of-pocket costs are anticipated to be greater than $100, you will be contacted before the test is started. q2. how does genetic testing work? The genetic test is done using a blood or saliva sample. Your sample is sent overnight in a special kit to Ambry Genetics (this is all coordinated by your healthcare provider). Once your sample arrives at Ambry, your BRCA1 and BRCA2 genes are analyzed. Everyone has these genes they each have a specific role in your body. The genetic test looks for any mutations that cause an increased risk of cancer. q3. can genetic testing results be used against me? The Genetic Information Nondiscrimination Act (2008) prohibits discrimination by health insurance companies and employers based on genetic information. Your state may have additional, more comprehensive laws in this area. q4. if i previously had cancer, do i need genetic testing? BRCA1/2 genetic testing is most useful when first performed in a family member who has already had breast or ovarian cancer. Results can provide an explanation for why the cancer occurred, and, more importantly, can provide information about future cancer risks. Genetic test results can change your ongoing medical management and can help your family members understand their risk of developing cancer. q5. how should i tell my relatives about my genetic test results? Genetic test results may be shared in a number of ways including by telephone call, visiting in person, letter, or email. It can sometimes be challenging because genetic testing is a very personal process, and everyone reacts to this type of news differently. Your healthcare provider may be able to help you come up with a plan to tell your family members, in a way that works best for all of you.

Test Result and Recommendations To be completed by you and your healthcare provider when you receive your genetic test results and medical management recommendations test result No mutation detected Positive for a mutation in gene Variant of unknown significance in gene recommendations for you recommendations for family members Genetic testing not appropriate for family members Genetic testing recommended for family members

Resources for Patients These and other resources can help build a sense of community and aid in answering some common questions. bright pink brightpink.org facing our risk of cancer empowered (force) facingourrisk.org susan g. komen breast cancer foundation komen.org young survival coalition youngsurvival.org national ovarian cancer coalition ovarian.org genetic information nondiscrimination act information ginahelp.org Find a Genetic Counselor national society of genetic counselors nsgc.org About Ambry innovation Ambry is a leading provider of diagnostic genetic testing, with years of experience using next generation sequencing technologies. expertise Since 2001, Ambry has performed hundreds of thousands of genetic tests and identified more than 45,000 mutations in greater than 500 different genes. ambry genetics 15 Argonaut Aliso Viejo, CA 92656 (866) 262-7943 info@ambrygen.com For more details about these tests, visit ambrygen.com 50339.1486_v1