BRCA1, familial breast-ovarian cancer susceptibility 1

The use of oral contraceptive pills (birth control pills) leads to a decreased risk of developing ovarian cancer. More specifically, studies have shown that the use of birth control pills reduced the risk of ovarian cancer by up to 45-50% in BRCA1 mutation carriers. That being said, some studies suggest that using birth control may increase the risk for breast cancer. Other research shows that birth control pills prescribed today do not increase early-onset breast cancer risk for women with BRCA1 gene mutations since nowadays pills contain a lower dose of estrogen. There are many different types of oral contraceptive pills, and the risks differ based on the specific formula. The benefits of oral contraceptive use may outweigh the potential negative consequences for some women. It is important to talk with your physician about what is right for your health.

If you have a positive result after genetic testing, other family members are at risk to have the same genetic change. First-degree relatives (siblings, children, and parents) have a 50% chance to have the same genetic change. Second-degree relatives (nieces/nephews, aunts/uncles, grandparents, grandchildren, and half siblings) have a 25% chance to have the same gene mutation. It is recommended that relatives be informed of their risk. Whether testing is right for them is a personal decision. Also, BRCA1/2 testing is not generally recommended for people under 18 years of age.

Other people with Hereditary Breast and Ovarian Cancer Syndrome can be found through these online support groups:

People with Hereditary Breast and Ovarian Cancer (HBOC) syndrome should be managed by a multidisciplinary team with expertise in caring for people with this condition. The team may include specialists such as a gynecologist, a medical oncologist, a breast surgeon, a gynecologic oncologist, a specialized nurse practitioner, and a genetic counselor. Some cancer centers may have specific programs for individuals with hereditary cancer risk.

People with HBOC syndrome should see a genetic counselor. A genetic counselor can help to further explain HBOC syndrome and answer any questions. A genetic counselor can also help to make any appropriate referrals to specialists. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Families that have multiple diagnoses of breast and/or ovarian cancers may have Hereditary Breast and Ovarian Cancer (HBOC) syndrome due to a change in the BRCA1 gene. Pancreatic cancer and prostate cancer are also found in families with BRCA1 gene mutations. Cancer diagnoses tend to occur at younger ages in individuals with a BRCA1 gene change. A diagnosis of breast cancer under age 50 is considered to be younger than expected in the general population. A diagnosis of breast cancer in a male, individuals with multiple BRCA1-associated cancers, and cancer in multiple generations on the same side of the family also increase the suspicion that there could be a mutation in the BRCA1 gene.

A genetic counselor can review a family history of cancer and help someone understand if their family may have a gene change causing HBOC. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Genetic changes in the BRCA1 and BRCA2 genes cause Hereditary Breast and Ovarian Cancer (HBOC) syndrome. There are numerous changes in these two genes that can cause HBOC. People of Ashkenazi Jewish ancestry are more likely to have three specific genetic changes:
• 185delAG (also known as 187delAG or c.68_69delAG) in the BRCA1 gene
• 5382insC (also known as 5382insC or c.5266dupC) in the BRCA1 gene
• 6174delT (also known as c.5946delT) in the BRCA2 gene
There are also specific BRCA1/2 gene changes that are common among individuals in other population groups.

There are key differences between analyzing the DNA from a tumor and analyzing DNA from your blood. It is not uncommon now to have DNA analysis (DNA sequencing) performed on a tumor sample. Outcomes can sometimes affect treatment options. Most of the genetic changes found in a tumor sample are new (somatic) changes. Somatic mutations are not present at birth, but rather they arise randomly later in life. Many somatic changes are made during the growth of a tumor. A BRCA1 gene mutation found in a tumor does not confirm that a person has Hereditary Breast and Ovarian Cancer (HBOC) syndrome.

Hereditary Breast and Ovarian Cancer syndrome is caused by germline mutations. These are genetic changes that we have in our DNA from birth, and we expect to find them in every cell in our body. DNA sequencing on blood or saliva samples can detect these germline mutations.

Hereditary Breast and Ovarian (HBOC) syndrome is a cancer condition caused by genetic changes in the BRCA1 or BRCA2 genes. Genetic changes in these genes can be passed from parent to child. In other words, HBOC syndrome runs in families. HBOC syndrome is the most common cause of both hereditary breast and hereditary ovarian cancer. People with a genetic change in a BRCA1 or BRCA2 gene have an increased risk for certain types of cancers, including breast, ovarian, prostate, and pancreatic cancers and melanoma. Both men and women can have HBOC syndrome.

Additional and accurate information about HBOC can be found on specific websites including:
1. The "Facing Our Risk of Cancer Empowered" (FORCE) advocacy group’s resources for people living with an increased risk of HBOC on their Understanding BRCA and HBOC website.

2. For healthcare providers, an expert summmary on HBOC can be found on the GeneReviews for HBOC.

Genes act as the instructions for the body. We all have two copies of the BRCA1 gene. We inherit one copy from our mother and one copy from our father. BRCA1 is a tumor suppressor gene. When working properly, the BRCA1 genes help to reduce cancer risk. People with Hereditary Breast and Ovarian Cancer (HBOC) syndrome have a gene change (mutation) in one of their BRCA1 genes that causes the gene not to work properly. A nonworking copy of the BRCA1 leads to increased risk for cancer.

Sometimes genetic testing shows a change in the BRCA1 called a "variant of unknown significance" or a VUS. This means that a genetic change was found that we do not fully understand. In other words, this genetic change may cause Hereditary Breast and Ovarian Cancer (HBOC) syndrome or it may be normal variation. We need more data to be sure. A genetic counselor or geneticist can help explain what this result means. Over time, scientists may learn more about variants of unknown significance. If someone has a VUS in the BRCA1 gene they should check with their healthcare provider on an annual basis for updates on the VUS.

A positive test result means that a genetic change was found in the BRCA1 gene that leads to increased risk for cancer. The cancers most commonly associated with BRCA1 gene changes are breast cancer in women and men, ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. A positive test result may change recommendations for cancer risk management. It is also recommended that individuals inform their relatives if they receive a positive result so that they can consider genetic testing themselves. If an individual tests positive for a gene change their first-degree relatives (parents, siblings, and children) have a 50% chance to have the gene change and second-degree relatives (half-siblings, aunts, uncles, nieces, nephews, and grandparents) have a 25% chance to have the gene change.

A negative genetic test result means no genetic changes were identified in the BRCA1 gene. A negative genetic test result will mean different things to different people.

Unfortunately, there are not good screening methods for ovarian cancer. For women, a prophylactic salpingo-oophorectomy (removal of the ovaries and fallopian tubes), can reduce the risk of ovarian cancer by 96%. This is why healthcare providers will more strongly recommend consideration of a bilateral salpingo- oophorectomy for women around 35-40 years of age who are done having children, or 40-45 years of age for women who have had a bilateral mastectomy. Healthcare providers may also recommend using medication, like birth control pills, to reduce ovarian cancer risk.

In general, increased breast cancer screening may detect breast cancer at an earlier, more treatable stage. Increased breast cancer screening for women commonly involves clinical breast exams and an annual mammogram and breast MRI. Men who carry a BRCA1 mutation should receive annual clinical breast exams.

There are also options to lower the risk for breast and ovarian cancers. These options may include risk-reducing medications like Tamoxifen or preventive (prophylactic) surgery. Surgery is not for everyone and is a very personal choice. For women, a bilateral risk-reducing mastectomy (removal of both breasts) can greatly reduce the risk of developing breast cancer. A prophylactic salpingo-oophorectomy (removal of the ovaries and fallopian tubes), can also lower the risk for breast cancer in premenopausal women.

The main symptom or feature of Hereditary Breast and Ovarian Cancer syndrome is an increased risk to develop cancer. The risks are highest for female breast cancer and ovarian cancer. The chance for a woman with a BRCA1 mutation to develop breast cancer by age 70 is between 55% and 65%. The chance for a woman with a BRCA1 mutation to develop ovarian cancer by age 70 is 39%. Men also have an increased risk to develop breast cancer and prostate cancer. More specifically, men with a BRCA1 mutation have a 1.2% risk to develop breast cancer by age 70. Both men and women also have an increased risk for pancreatic cancer.

Multiple studies have been done to estimate cancer risks in men and women with BRCA1 gene mutations. Therefore risk numbers may vary somewhat and these estimates may change over time as more information is learned about BRCA1-associated cancer risks. Talk to a genetic counselor or other medical professional with expertise in HBOC to learn more about BRCA1-associated cancer risks. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Prostate cancer screening is recommended for men who carry a BRCA1 mutation. Prostate cancer screening may be recommended to begin around age 40 for men with a BRCA1 gene mutation, which is a younger age than the screening recommendation for men in the general population. Men with a BRCA1 gene mutation should talk with their doctor about current screening guidelines.

Men should be tested for BRCA1 gene mutationsl. Men are just as likely to have a BRCA1 gene mutation as women. There are increased cancer risks for men as well. These include prostate, pancreatic, and male breast cancers. If a man has a BRCA1 gene mutation, he has a 50% chance to pass it down to each of his sons and daughters.

Most of the time genetic testing for HBOC syndrome is not recommended for people under the age of 18. For HBOC syndrome, screening does not begin until around 25 years of age so testing a minor will typically not affect their medical management. Numerous professional organizations, such as the American Academy of Pediatrics and the American College of Medical Genetics, support waiting until a person is at least 18 years of age to test for adult-onset conditions, such as HBOC syndrome. This allows individuals to choose for themselves as adults whether or not they want to have genetic testing.

If a mother has the BRCA test and a variant of uncertain significance was identified in the BRCA1 gene, there’s a 50% chance that a daughter’s test would show the same result as her mother’s, and a 50% chance that her test would have a normal result.

Each of us has thousands of genes that tell our bodies how to develop and function. Not all changes in these genes are bad. If a lab test finds a change in the BRCA1 gene, but can not say for sure whether the change increases the chance of developing cancer, then it is call a variant of unknown certainty (VUS). As more people get tested, the laboratory will gain more information about the VUS change and will either decide that it is harmless or that it does, in fact, pose a higher risk of cancer. In that case, the person’s cancer screening and risk management should be based on her own personal and/or family history of cancer.

When more information becomes available about that specific change or variant, it may be reclassified as pathogenic (disease-causing), likely pathogenic (likely disease-causing), likely benign (likely not disease causing), or benign (not disease causing). However, reclassification can take a long time and not all laboratories doing testing watch for new data available to change a VUS’s classification and/or issue new reports. For some perspective, more than 80 million genetic variants have been uncovered in the human genome, and for the most there is no clear understanding of their role in human health and disease. The best way to know if a VUS has been reclassified as disease causing or not is for the person with the test result to ask their doctor to double check with the laboratory. The doctor should ask the laboratory for a updated review of current information on the change and if the VUS will be or has been reclassified. For some genes such as BRCA1, websites have been created by laboratories that make it very easy for a doctor to find out if a VUS has been reclassified. Examples include: BRCA Share for BRCA1 mutations by Quest diagnostics.

For people who have been found to have a VUS in BRCA1 or BRCA2, they may also choose to participate in the the "Free the Data" project. "Free the Data" is a grassroots initiative which asks people who have had genetic testing for the BRCA1 and BRCA2 genes to share their results and health information with the "Free the Data" team so that they can enter them into ClinVar, an open-access database of mutations run by the NIH in order to gain a better understanding of hereditary breast and ovarian cancer. This step is important as not all testing laboratories enter their information into confidential, but publicly accessible databases like Clinvar where researchers can use them. The goal of the "Free the Data" movement is to understand more information about mutations and variants of unknown significance (VUS) in BRCA1 and BRCA2. Over time, the campaign hopes to expand to encompass all genes and all mutations, powering new research and better health for all. To learn more about the "Free the Data" movement and how people can be involve visit the Free the Data website.

We each have two copies of the BRCA1 gene in our bodies, one that we inherit from our mother, and the other that we inherit from our father. When we have children, we pass down just one copy of our BRCA1 gene. Imagine a mother with a variant of unknown significance in one of her copies of BRCA1 gene, and the other does not have any changes. This means that there is a 50% chance that a daughter inherited that change from her, but also a 50% chance that she did not inherit that change. In other words, there’s a 50% chance that a daughter’s test could show the same result as her mom’s, or a 50% chance that her test would have a normal result. The daughter’s cancer screening and risk management should also be determined based on her own personal and/or family history of cancer.

A genetic counselor or genetic nurse can help you understand your cancer risk and breast management based on your personal and family history.

Not every person with Hereditary Breast and Ovarian Cancer (HBOC) syndrome will develop cancer in his or her lifetime. In other words, HBOC syndrome is not completely penetrant. This condition also has variable expression, which means that not every person who develops cancer will develop the same type of cancer. Knowing there is an increased risk for developing certain types of cancer will help healthcare providers offer appropriate screening and risk reduction options.

There are some findings in a personal and family history that can be considered red flags of Hereditary Breast and Ovarian Cancer (HBOC) syndrome.

Newborn screening is performed soon after a baby is born. It ensures that all babies are screened for certain serious conditions at birth. Hereditary Breast and Ovarian Cancer syndrome is not one of the conditions included on newborn screening. In general, genetic testing for HBOC syndrome is not recommended for people under the age of 18. Furthermore, HBOC syndrome is not included on the Recommended Uniform Screen Panel (RUSP). The RUSP is created by the Health Resources and Services Administration and lists the conditions every baby should be screened for. States use this list to guide what conditions they include on newborn screening.

There are multiple testing options for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. If there is a known gene mutation in a family, targeted testing, also known as single site testing can be ordered. With targeted testing, the laboratory will only look for one specific genetic change instead of scanning the entire gene. This is generally the least expensive option offered by testing companies. In order to have targeted testing, you must provide a copy of your relative’s positive genetic test result so the laboratory knows what genetic change to test for.

There are also testing options when a gene mutation has not been identified in the family. Many laboratories offer complete analysis of the BRCA1 and BRCA2 genes. This analysis involves sequencing and deletion/duplication analysis of the BRCA1 and BRCA2 genes. For people of Ashkenazi Jewish ancestry testing for the three BRCA mutations that are most common in the Ashkenazi Jewish population is the recommended starting point. If none of the three common mutations are found additional testing may be considered.

There are several genes beyond BRCA1 and BRCA2 that can be associated with hereditary risk for breast and/or ovarian cancers. In some situations, testing for multiple genes may be more efficient and/or cost-effective. This type of testing is often referred to as multi-gene testing or panel testing. Cancer panels often include BRCA1, BRCA2, and other genes that are associated with hereditary cancer.

There are benefits, risks, and limitations to any type of genetic testing. It is important to have genetic counseling from a qualified healthcare provider to aid in this decision-making process. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

ClinicalTrials.gov provides up-to-date information on research being conducted. The following support groups may also have updated information on current research.

There is no treatment that can cure Hereditary Breast and Ovarian Cancer (HBOC) syndrome. However, there are options available to reduce the risk of developing cancer. These options include:

Cancer genetic counseling services are for both women and men who have concerns about their personal and/or family histories of cancer. Cancer genetic counseling is performed by specially trained healthcare providers who have knowledge in genetics, cancer, counseling, and hereditary cancer syndromes. These healthcare providers may be genetic counselors, doctors, genetics clinical nurses, or other healthcare professionals with formal training in genetics. The information from genetic counseling can help people at risk and their family members lower their risk for cancer and/or help detect cancer at an earlier, more treatable stage.

One online tool that can help someone find out if they should have genetic counseling is called the Breast Cancer Genetics Referral Screening Tool (B-RST™). B-RST™ was developed by a genetic counselor to help identify people who have a strong genetic (hereditary) risk for breast and/or ovarian cancer and would benefit from genetic counseling. Another online tool, called assessyourrisk™, was development by Bright Pink. Bright Pink is a national non-profit organization focused on prevention and early detection of breast and ovarian cancer in young women.

There are also several laboratory-sponsored tools available to determine if counseling and genetic testing may be appropriate. Some examples are:

Preimplantation genetic diagnosis (PGD) is available for Hereditary Breast and Ovarian Cancer syndrome if one of the parents is known to carry a BRCA1 mutation. PGD is performed on embryos produced through IVF. PGD allows for parents to only implant embryos into the mother’s uterus that do not have the BRCA1 gene mutation. PGD is still a very costly procedure though, and it is not guaranteed to lead to pregnancy every time.

Some labs may accept prenatal specimens for genetic testing if a parent is known to carry a BRCA1 mutation. With prenatal testing, the baby’s DNA is tested during the pregnancy to determine whether the baby has the BRCA1 gene mutation. The procedures available to obtain the baby’s DNA during a pregnancy are associated with a risk of pregnancy loss. Prenatal testing is not commonly utilized or recommended for adult onset conditions like Hereditary Breast and Ovarian Cancer syndrome.

There is much debate over this question. Use of hormone replacement therapy (HRT) can increase the risk for breast cancer. Many physicians are nervous to prescribe HRT to a woman whose risk for breast cancer is already high. The benefits of HRT after prophylactic oophorectomy can greatly improve quality of life for some women though. Some research has shown that prophylactic oophorectomy reduces the risk for breast cancer even with HRT use. More specifically, one study demonstrated that short-term use of HRT following an oophorectomy did not significantly alter breast cancer risk. There are many factors to discuss with your healthcare provider before deciding whether you should use HRT.

We all have two copies of the BRCA1 gene. We inherit one copy from our mother and one copy from our father. BRCA1 is a tumor suppressor gene. When working properly, the BRCA1 genes help to reduce cancer risk. People with Hereditary Breast and Ovarian Cancer (HBOC) syndrome have a gene change (mutation) in one of their BRCA1 genes that causes the gene not to work properly. A nonworking copy of the BRCA1 leads to increased risk for cancer. If a parent has Hereditary Breast and Ovarian Cancer syndrome, there is a 50% chance that each of his or her children will also have HBOC syndrome. This is called autosomal dominant inheritance.

There are multiple ways to financially support research related to Hereditary Breast and Ovarian Cancer syndrome.
Cancer Research UK allows you to choose what research project you fund. People may also choose to donate to support groups, like [link url="www.brightpink.org” target=”_blank”>Bright Pink, FORCE, Willow, and LIVESTRONG.

There are several laboratories that offer diagnostic testing for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. There are multiple types of tests to choose from as well. Bright Pink, a national non-profit organization focused on prevention and early detection of breast and ovarian cancer in young women, has created a website, called exploreyourgenetics, that guides you through testing options. A genetic counselor can explain the testing options and help coordinate testing. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

A genetic counselor can help to further explain Hereditary Breast and Ovarian Cancer syndrome (HBOC) and other hereditary cancer conditions and answer any questions. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website. You may also find medical professionals knowledgeable about HBOC at your local or regional cancer center. Some cancer centers may have hereditary cancer risk programs available.

ClinicalTrials.gov provides up-to-date information on research being conducted.

Many support groups have information about current research and clinical trials on their websites.

The "Free the Data" movement is a grassroots initiative which asks people who have had genetic testing for the BRCA1 and BRCA2 genes to share their results and health information with the "Free the Data" team so that they can enter them into ClinVar, an open-access database of mutations run by the NIH in order to gain a better understanding of hereditary breast and ovarian cancer. This step is important as not all testing laboratories enter their information into confidential, but publicly accessible databases like Clinvar where researchers can use them.

The goal of the "Free the Data" movement is to understand more information about mutations and variants of unknown significance (VUS) in BRCA1 and BRCA2. This information will hopefully help doctors find better treatment options for those with those mutations.

Over time, the campaign hopes to expand to encompass all genes and all mutations, powering new research and better health for all.

To learn more about "Free the Data" and ClinVar there is information through the NCBI.

Hereditary Breast and Ovarian Cancer syndrome is the most common cause of both hereditary breast and hereditary ovarian cancer. Less than 1% of the general population (1 in 400 people) has a genetic change, or mutation, in BRCA1/2, which causes HBOC syndrome. BRCA1/2 mutations are more common in individuals of Ashkenazi Jewish ancestry. More specifically, around 2.5% of people from the Ashkenazi Jewish population (1 in 40 people) carry a BRCA1/2 mutation.

Joining a national or international support group link FORCE, Bright Pink, Willow, or Sharsheret is a great way to get new information about Hereditary Breast and Ovarian Cancer (HBOC) syndrome.

Receiving cancer screening and treatment in a cancer center is another way stay up-to-date with current management guidelines. Some cancer centers may have hereditary cancer risk programs available.

In 2016, knowing that you have a BRCA1 mutation and breast cancer does not currently change the type of chemotherapy doctors suggest before surgery (neoadjuvant chemotherapy). Determination of which pre-surgery chemotherapy to use is based on the doctor’s judgment. However, there are laboratories developing very specialized genetic testing on tumors to help doctors make decisions on which chemotherapy to use. An example of one such company is Bioarray Genetics who have developed an RNA-based predictive test (BA100) that is hoping to be able to identify breast cancer patients who will and will not realize a complete response to the standard-of-care taxane-based pre-surgical chemotherapy. More information on the test in development can be found on the Bioarray Genetics website.

Beyond pre-surgical chemotherapy, There are studies looking at post-surgery breast cancer treatment in individuals diagnosed with HER2 negative breast cancer who also have inherited mutations in the BRCA1 or BRCA2 genes. These studies are trying to figure out if taking medications such as Olaparib, an FDA-approved targeted therapy that inhibits the action of PARP (poly adenosine diphosphate-ribose polymerase), can reduce the risk of breast cancer recurrence after standard therapy in patients with BRCA1 or BRCA2 mutations. Several studies in other cancers, such as ovarian cancer, have shown that olaparab is effective in patients with BRCA1 or BRCA2 gene mutations. More information about this study and others like it are available Clinicaltrials.gov

All genetic testing laboratories should accept blood samples and many also accept saliva samples. Saliva sample tests are just as reliable as blood sample tests. All the cells in a person’s body have the same DNA, so it does not matter if you test blood cells or cells found in saliva.

Hereditary Breast and Ovarian Cancer syndrome is caused by mutations, or genetic changes, in either the BRCA1 or BRCA2 genes. There are also other hereditary breast cancer syndromes. For example:

There are not any specific screening guidelines for pancreatic cancer, but screening may be individualized based on the cancers in the family.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is also known as BRCA-Related Breast and/or Ovarian Cancer syndrome. HBOC syndrome is often referred to by using the names of the genes associated with this condition. These genes include BRCA1 and BRCA2. Sometimes the two gene names are combined together to BRCA1/2, or simply referred to as BRCA. Some people also call BRCA1 and BRCA2 the "BRACA" genes. BRACA was the name of one of the first genetic tests to look at the BRCA1 and BRCA2 genes.

There are wonderful support groups for people with Hereditary Breast and Ovarian Cancer syndrome. Some examples include: