Hereditary Breast and Ovarian Cancer: What you need to know about risk
by Dr. C.H. Weaver M.D. 8/2020
What is hereditary breast and ovarian cancer syndrome?
Hereditary breast and ovarian cancer (HBOC) is one of the most commonly inherited breast and ovarian cancer syndromes. HBOC is due to mutations, or changes, in the BRCA1 and BRCA2 genes, also called the BRCA genes. (BRCA1and BRCA2 stand for breast cancer gene 1 and breast cancer gene 2.) About 1 in 500 people in the United States has HBOC syndrome due to mutations in the BRCA1 or BRCA2 gene.
People with HBOC have an increased lifetime risk of developing certain types of cancers. As the name HBOC implies, those cancers include breast and ovarian cancers. An individual with HBOCs has up to an 80 percent lifetime risk of developing breast cancer and up to a 40 percent lifetime risk of developing ovarian cancer. Cancers that develop as a result of the HBOC syndrome generally occur at an earlier age compared with those that develop in people who do not have the syndrome; a woman can develop more than one breast cancer in her lifetime if she has this condition. Other cancers associated with HBOCs include prostate cancer, male breast cancer, fallopian tube cancer, pancreatic cancer, and melanoma (skin cancer).
What causes HBOC?
HBOC is caused by a genetic mutation called a deleterious mutation, or a disease-causing mutation, in either the BRCA1 or the BRCA2 gene.
To understand the HBOC syndrome, it is helpful to know a few basics about genetics. A gene is a hereditary unit of DNA. Genes carry directions to cells and tell them to make specific proteins that perform and regulate all functions of the body. Genes are capable of replicating themselves at each cell division.
A mutation is a change in the usual DNA sequence of a particular gene. Mutations can be beneficial, harmful, or neutral. Many diseases, including cancer, begin in the genes. Genetic mutations can be inherited from a parent or can be a random event that occurs in one single cell during cell division—or even in response to environmental factors and exposures. In the case of HBOC, we know that there is a deleterious mutation that causes the BRCA1 or BRCA2 gene to work incorrectly.
How would I know if my family has HBOC?
First, awareness of your family and personal health history is key. We know that families with hereditary cancer syndromes often have a family history that includes multiple generations affected by specific types of cancer that fit a certain pattern. And these cancers are often diagnosed at younger ages. Individuals in these families will often develop multiple cancers in their lifetime.
Red flags in a family history that might indicate HBOC include breast cancer diagnosed under the age of 45; ovarian cancer diagnosed at any age; breast and ovarian cancer diagnosed in the same woman; bilateral breast cancer diagnosed in a woman of any age; male breast cancer in any member of the family; and Ashkenazi Jewish ancestry (individuals of Ashkenazi Jewish ancestry have a much higher chance of carrying a mutation in either their BRCA1 or BRCA2 gene).
If I think my family may have HBOC, what steps should I take?
First meet with a genetic counselor. A professional will have the tools to take a good family history and determine whether you meet criteria for genetic testing and what type of genetic testing you would need.
To prepare for a meeting with a genetic counselor, make sure that you have spoken with your family and understand your family history; the genetic counselor will take a detailed family history as a first step. Next, the genetic counselor will review the history for certain patterns in the family, including early onset of cancers and multiple cancers in the family (especially breast, ovarian, fallopian tube, pancreatic, melanoma, and prostate cancers). Based on these patterns, genetic testing may be recommended. In some cases, it may not be you who is ultimately recommended for genetic testing but rather another family member who would be a better candidate. This may be a relative who has already been diagnosed with a cancer, as it is more likely that a genetic mutation would be revealed in someone who already has cancer.
What does genetic testing involve?
Genetic testing is a simple process: it involves either a blood draw or a saliva sample, which is then sent to a genetic laboratory, where BRCA1 and BRCA2 genes are examined for any mutations or changes that would cause them not to work correctly. With new genes being discovered all the time, we are finding that the BRCA1 and BRCA2 genes are not the only genes that cause hereditary cancer conditions. The genetic counselor may recommend that you undergo panel testing, wherein multiple genes are tested to see if you carry various known mutations (including BRCA1 and BRCA2) that might lead to cancer. Panel testing is a more efficient method to carry out genetic testing and is becoming the standard process.
What do my test results mean?
There are a variety of results you may receive after undergoing genetic testing. The following is a brief summary of potential outcomes and what they mean.
Positive. A “positive” result means that a deleterious mutation has been discovered in either your BRCA1 or BRCA2 gene, which is the cause of your and your family’s cancers. This result would mean that you have HBOC.
Negative. A “negative” result means that no mutation was discovered in your BRCA1 or BRCA2 gene, although this result does not always mean that you are free of HBOC. As of right now, genetic testing is not 100 percent accurate, and there are instances in which mutations are missed due to limitations of genetic testing. It is important that you meet again with the genetic counselor to discuss whether there is additional recommended testing or if, based just on your family history, there are certain types of screening that he or she would recommend even if you have a negative test result.
Variant of uncertain significance (VUS). A “VUS” result means that a mutation was found but it is unclear what that mutation does to the gene; we don’t know if it changes the function and causes it not to work or if it does nothing to the gene at all. If you receive this result, the genetic counselor or medical provider will generally plan to continue to monitor your health, as a definitive diagnosis is not possible. As a patient it is important that you continue to follow up with the genetic counselor to track any changes or reclassifications in that VUS.
You have HBOC. What’s next?
If you do find out that you have HBOC, there are steps you can take to reduce your risk of developing related cancers.
Breast cancer screening. Women who have tested positive for HBOC should become very familiar with their breasts through breast self-exams (recommended beginning at age 18) so that they can be aware of any changes as soon as possible. In addition, women with HBOC are advised to undergo an annual clinical breast exam, mammogram, and breast magnetic resonance imaging (MRI) scan, starting at age 25. The recommended schedule for these screening tools is to alternate the mammogram and MRI every six months.
Ovarian cancer screening. Ovarian screening tools are limited, and there is no consensus as to their value; however, despite conflicting recommendations, some physicians still recommend ovarian cancer screening. Current screening options include transvaginal ultrasound and a CA- 125 blood test, which may reveal a specific marker in the blood associated with ovarian cancer. Experts agree that it is most important to be aware of the often subtle signs and symptoms of ovarian cancer. Understanding these vague early indicators of ovarian cancer provides a better chance of catching ovarian cancer at an earlier stage.
Male screening guidelines. Men with HBOC should have a baseline mammogram so that any changes in breast tissue are apparent in any follow-up screening; in addition, prostate cancer screening is recommended, starting at age 40.
Skin cancer screening. Men and women with HBOC—especially those with a BRCA2 mutation—should undergo annual skin exams with a dermatologist to screen for melanoma.
Chemoprevention. Chemoprevention is the use of drugs to prevent cancer. The chemopreventive drugs tamoxifen or Evista® (raloxifene)—drugs that are known as selective estrogen receptor modulators*—may be used to reduce the risk of breast cancer in women at high risk of the disease. Oral contraceptive drugs may also be used as chemopreventive agents, as they have been found to reduce the risk of ovarian cancer.
Risk-reducing surgery. A bilateral mastectomy, or the removal of both breasts, can reduce a woman’s risk of breast cancer by 90 percent. (A woman’s risk of breast cancer cannot be completely ruled out because some breast tissue may remain after the bilateral mastectomy.)
A bilateral salpingo-oophorectomy, a surgical procedure to remove a woman’s fallopian tubes and ovaries, is another risk-reducing surgery. This procedure is typically recommended for premenopausal women who have completed child bearing or by the age of 40. When a woman chooses to have her ovaries and fallopian tubes removed and the procedure is completed before menopause, she dramatically reduces her risk of ovarian cancer by at least 90 percent and reduces her risk of breast cancer by about 50 percent.
HBOC Is A Family Affair
It is very important that you share your genetic information with your family members, as they are also at risk of HBOC. There are things that they can do to prevent or greatly reduce their risk of cancer if they know that they have the condition (chemoprevention, cancer screening, risk-reducing surgeries). Even if family members have already had cancer, it is important that they be informed of genetic-testing results that may affect them because there are certain clinical trials investigating preventive and treatment strategies that could provide benefit.
Results of genetic testing can be shared via e-mail, a phone call, the family communication tool KinTalk.org, or face-to-face, depending on your comfort level. When you share the results, it is a good idea to also recommend that family members see a genetic counselor.
Join the conversation and connect with others dealing with hereditary cancers in the CancerConnect Genetic testing and cancer screening community.
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