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Inherited Risk: The BRCA Gene Explained

Medically reviewed on Apr 16, 2018 by L. Anderson, PharmD.

What are BRCA1 and BRCA2 Genes?

Genes are passed from parent to child and define how we look and how our body functions. The BReast CAncer susceptibility gene (BRCA1 and BRCA2) are genes in our body that slow down cancer growth by repairing damaged genetic material (DNA).

However, if these genes are altered through a mutation the DNA damage may not be repaired. Cancer cells can grow more easily with mutations in either the BRCA1 or BRCA2 genes. Mutated BRCA genes can be inherited from mother, father, or both parents.

Women with a mutation in the BRCA1 or BRCA2 gene have a higher risk of developing:

There is also a smaller risk of developing other cancers due to this mutation in women, such as fallopian tube cancers, peritoneal cancers, and pancreatic cancers.

Men may also have BRCA mutations and are at higher risk for:

Should I Be Worried About Inherited Breast or Ovarian Cancer?

In general, only about 5 to 10 percent of breast or ovarian cancers are due to inherited risks from your mother or father. Most cancers, including breast and ovarian cancers, are due to mutations that occur throughout your lifetime due to environmental toxins or chemicals, viruses, or some other unknown cause.

However, if you have strong family history of breast or ovarian cancer (mother, sister, daughter) or have a man in your family (father, brother, son) who has had breast cancer or prostate cancer you should be sure to explain this to your doctor, who can assess if you need genetic counseling. This is especially important if the family member was less than 50 years of age at the time of diagnosis.

Multiple family members with these cancers and a single family member with multiple types of cancer may mean there is genetic link. Pancreatic and colon cancer can also be inherited through genes.

Why Is BRCA Testing Done?

Knowing if you have BRCA1 or BRCA2 mutation will give you the opportunity, in consultation with a certified genetic counselor, to make decisions about how to lower your risk for cancer.

Testing positive for BRCA gene mutation is not common. According to the US Preventive Services Task Force (USPSTF), these mutations occur in roughly 1 in 300 to 500 women (0.2 to 0.3%). However, in people with immediate family members who have been identified with BRCA gene mutations or have a pattern of certain cancers, testing might make sense.

Not everyone needs a BRCA test; in fact, most people do not. Your primary care physician will assess your need for genetic counseling. After meeting with the certified genetic counselor, testing may be recommended for those who have a personal or family history of breast, ovarian, or other cancers.

Should I Consider Getting Tested for the BRCA Gene?

The best way to determine if you should be tested for BRCA1 or BRCA2 mutation is to first talk with your primary care provider. There are special tools your doctor can use to help determine the need for genetic counseling.

Actions from BRCA gene testing might include:

BRCA testing can be an emotional roller coaster for some. However, for many, knowing their predicted risk level and determining a path forward is a relief.

BRCA status can also be useful information for one's children -- both boys and girls -- when they grow older. In someone who has a BRCA mutation, their child will have a 50% chance (1 in 2) of inheriting the gene. As adults, your child may decide to undergo genetic counseling. BRCA testing is not recommended for children under 18 as pediatric cancers associated with these mutations are uncommon.

Should You Consider BRCA Gene Testing?

Screening tools are now available that health care providers can use to determine your likelihood of having a BRCA1 or BRCA2 gene mutation.

These tools assess individual and family risk factors, including:

  • A diagnosis of ovarian cancer at any age
  • Breast cancer diagnosis before age 50, or before 60 years if triple negative breast cancer
  • Cancers in both breasts
  • Breast and ovarian cancers in same woman or family
  • Multiple breast cancers in close members (grandmother, mother, sister) of a family
  • Two or more BRCA1 or BRCA2-related cancers in one or more family member
  • Family history of male breast cancer
  • Ashkenazi Jewish (Eastern European) ethnicity with a family history of breast, prostate, pancreatic or ovarian cancer

Roughly 10% to 30% of women under 60 years who have “triple-negative” breast cancer (cancer that does not have estrogen, progesterone and HER2/neu receptors) will have BRCA1 or BRCA2 gene mutation.

How Is BRCA Testing Done?

It is preferable that BRCA testing be done in the youngest family member that has been diagnosed with cancer, typically breast or ovarian.

If a BRCA mutation is not found, testing of other family members without cancer is not usually helpful. However, if it is not possible to test a family member, and your risk is deemed high, BRCA testing is an option for you.

How do you prepare? The actual BRCA test is fairly straightforward and simple; a DNA sample from a blood test or a saliva test is used. Most often a blood sample is drawn from your arm. The sample is sent to a laboratory and the results can take several weeks. When your results are available, you will meet with your genetic counselor to discuss the results and determine next steps.

How Much Will Having a BRCA Gene Mutation Increase My Cancer Risk?

To determine how much impact a positive BRCA gene mutation might have, it's often helpful to compare with cancer risks in the general population first.

Overall, in the general population, 12.4% of women (12.4 out of 100) will develop breast cancer in their lifetime, and 2.7% will die from the disease. These means that a woman born today has roughly a 1 in 8 chance of being diagnosed with breast cancer during her lifetime. Another way to look at this, however, is that the chance that she'll never have breast cancer are about 7 in 8, or over 87%. Ovarian cancer is much lower in the general population: 1.4% of women will develop ovarian cancer and 1% will die.

The rates of breast cancer are much higher in women who have a positive BRCA test, In women who test positive for either BRCA gene mutation, their risk of breast cancer occurrence by age 70 ranges from 45% to 70%. In general, this means that out of a sampling of 100 women with a positive BRCA gene, 45 to 70 women will develop breast cancer in their lifetime. Specific mutations in the BRCA1 gene increase the ovarian cancer risk to 39% by age 70, and BRCA2 mutation raise the ovarian risk to 10% to 17%. Studies have shown the rates of BRCA1 and BRCA2 mutations can be higher in Ashkenazi Jewish women.

Based on these estimates supplied from the USPTSF, it's easy to see that women with BRCA mutations have a much higher risk for breast and ovarian cancers compared to the general population.

My BRCA Test is Positive. Now What?

A genetic counselor will help you to understand your tests results when they are available. Having a positive test does not mean you will definitely develop cancer; only that your risk is increased.

Based on many different factors, including:

  • Your family history
  • Age
  • Overall health
  • Prior treatments
  • Surgical history
  • Personal preferences

your options to lower cancer risk might include:

  • Earlier, more frequent, or more intensive cancer screenings
  • Use of certain medications to lower your risk, such as [tamoxifen](https://www.drugs.com/tamoxifen.html) or [raloxifene](https://www.drugs.com/mtm/raloxifene.html) (Evista)
  • Preventive (prophylactic) surgery such as breast removal (mastectomy) or removal of ovaries and fallopian tubes (salpingo-oophorectomy).
A combination of the above options might be used, too. Specific details associated with the above options are detailed on the following slides.

Options: More Frequent or Intensive Screenings

More frequent screenings are one option to help lower the risk from dying from certain cancers linked with a BRCA gene; however, screenings won't lower your risk for getting cancer.

Screenings typically include:

  • mammograms started at an earlier age
  • mammograms and breast MRIs alternated every 6 months
  • a monthly self-breast exam should also be performed.

Screening for ovarian cancer is not optimal and does not have a high success rate of identifying disease. However, ovarian cancer screening may be offered as an option, using a blood test known as CA-125 combined with a pelvic ultrasound every 6 months in women at high risk.

A CA-125 test isn't used for ovarian cancer screening in all women becuase it is not precise enough and other non-cancerous events can raise a CA-125 level, such as menstruation or uterine fibroid tumors.

Option: Drug Therapy to Reduce Breast Cancer Risk

Use of certain medications can lower the risk of developing breast cancer, although the effects in BRCA mutations are less well-known:

Tamoxifen and raloxifene (Evista) are approved to lower the risk of breast cancer occurrence in women in the general population at risk, but the effect in women with BRCA mutations is not fully known. They are classified as selective estrogen receptor modulators (SERMs). These drugs block estrogen in breast cells to help lower breast cancer risk.

In the general population, tamoxifen and raloxifene can lower the risk of developing breast cancer by about 40% to 50% in women at risk. Both drugs are approved by the FDA for use in high risk women, but not specifically for women with BRCA mutations. However, smaller studies have shown that tamoxifen may help lower the risk in women specifically with a BRCA2 gene mutation, but more studies are needed before it is routinely recommended.

Other preventive medications for the general population might include the aromatase inhibitors (AIs) exemestane (Aromasin), anastrozole (Arimidex), and letrozole (Femara), which may help reduce the chance of breast cancer in postmenopausal women at high risk. AIs are used mainly to treat women with hormone receptor-positive breast cancer. These drugs are not specifically FDA-approved for primary prevention, but may be useful in women who cannot use a SERM. In addition, in women with BRCA mutations, it is not known if these drugs would be helpful.

Hormonal contraceptives such as the pill have also been shown to reduce ovarian cancer risk by about 50%, in the general population and in women with a BRCA mutation. However, there is a concern that hormonal contraceptives may also increase the risk of breast cancer, particularly in BRCA1 carriers.

Option: Preventive Surgery

Preventive (prophylactic) surgery such as:

can substantially lower the risk for breast or ovarian cancer in women with BRCA genes.

With a prophylactic mastectomy (removal of both breasts), breast cancer risk can be reduced by at least 90 percent, according to studies.

In premenopausal women having a prophylactic salpingo-oophorectomy (removal of fallopian tubes and ovaries), the risk of ovarian and fallopian tube cancer is reduced by roughly 80% and breast cancer risk is lowered by at least half.

What If My BRCA Test Is Negative?

You should discuss any result, positive or negative, with your genetic counselor. Each case is individual, but in general, a negative BRCA test means you do not have a BRCA gene mutation.

However, that does not mean that you cannot get cancer either due to another hereditary risk factor or some other unknown reason. BRCA testing does not test for every genetic mutation.

If one of your close family members has a BRCA mutation, and your test is negative, this means that your risk for cancer is equivalent to the general population.

Is My Genetic Information Private?

One concern you may have about going forward with any type of genetic testing is your privacy. Your genetic information is protected under federal and state laws, and, as of April 2018, you cannot be denied health insurance based on your results.

The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits health insurance and employers from using your genetic information. Your employers cannot fire you due to genetic testing, and your health insurance can't raise your rates or deny you coverage.

However other insurance, such as life, disability, or long-term care insurance may not be subject to these privacy laws. You should consider discussing this important topic with your genetic counselor, who will have updated privacy laws and guidelines.

You are able to submit genetic testing anonymously with a code and pay cash for the test, if privacy is a top concern for you.

First Home Test for Three BRCA Breast Cancer Genes Now Available

In March 2018, the FDA approved the first home, direct-to-consumer test to detect BRCA gene mutations associated with breast, ovarian and prostate cancer. But it's not a test to be used by the general population who may be at risk of the most common BRCA1/BRCA2 mutations. The test, from 23nMe, is called the Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants) and analyzes DNA from saliva collected by the user.

The mutations found by this test are most common in people of Ashkenazi (Eastern European) Jewish descent. The three mutations detected by the test occur in about 2% (2 out of 100) of Ashkenazi Jewish women, but occur rarely in 0 to 0.1 percent of other ethnic groups, according to the National Cancer Institute. A negative test result could still mean that a person has an increased risk of cancer due to other BRCA gene mutations or other cancer-related gene mutations.

According to the FDA:

  • The test should not be used by consumers or health care providers to decide on any treatments, including anti-hormone therapies and preventive removal of breasts or ovaries. Confirmatory testing will be needed.
  • Decisions for treatment also require genetic counseling.
  • The test is not a substitute for regular cancer screenings, or counseling on genetic and lifestyle factors that can increase or decrease cancer risk.

Lynparza Use Expanded for Breast Cancer with BRCA Mutations

BRCA genes normally work to repair damaged DNA and prevent tumor development. Today, treatments specifically for breast cancer susceptibility gene (BRCA) mutation in breast cancer are making headway. But remember, only 5% to 10% of patients with any type of breast cancer have a BRCA gene mutation.

In January, 2018 the FDA expanded the use of Lynparza (olaparib tablets) as the first approved treatment for patients with metastatic breast cancer with a BRCA mutation. Lynparza, also approved to treat BRCA ovarian cancer, is the first poly ADP-ribose polymerase (PARP) inhibitor approved to treat breast cancer. Patients are determined to be candidates for Lynparza treatment based on an FDA-approved genetic test, called the BRACAnalysis CDx.

In clinical studies of 302 patients with HER2-negative metastatic breast cancer with a germline BRCA mutation, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Common side effects in these studies with Lynparza included altered levels of red and white blood cells (anemia, neutropenia, leukopenia), nausea, fatigue, vomiting, common cold (nasopharyngitis), and respiratory tract infection, among other side effects. Serious side effects include inflammation in the lungs (pneumonitis) and development of certain blood or bone marrow cancers.

Is BRCA Testing Covered By Insurance?

The costs associated with BRCA testing can be substantial; however, if you meet the criteria to be at risk for a BRCA gene mutation, your insurance should cover your costs. In fact, The Affordable Care Act considers genetic counseling and BRCA1 and BRCA2 mutation testing for individuals at high risk a covered preventive service; how this might change going forward with the repeal of the ACA is not known yet.

Talk to your primary care provider about utilizing an in-office questionnaire to determine if you might be a candidate for genetic counseling and possible BRCA testing. Your insurance carrier can provider further criteria to your counselor or you to determine your share of costs, if any.

If you were to fully pay out-of-pocket for BRCA testing, the cost could run from $250 to $500, as several companies now offer BRCA testing. Testing for many breast cancer-related genes may drive the cost up. Test results typically take 2 to 4 weeks.

Medicare in the U.S. covers BRCA1 and BRCA2 testing for women who have signs and symptoms of breast, ovarian, or other cancers that are related to these mutations, but will not pay if you have no signs or symptoms.

If you cannot afford BRCA testing, but you need it, speak to your healthcare provider who can direct you to possible financial resources. Some genetic testing companies may offer it at no cost if you meet certain criteria.

Typically, direct-to-consumer testing is not covered by insurance, but it might worth checking with your insurance company.

BRCA Gene Testing: Find Support

You may remember hearing about BRCA gene testing back in 2013 when American actress, director, and producer Angelina Jolie opened up about her decision to have a mastectomy in The New York Times.

Jolie wrote an eloquent op-ed entitled "My Choice." She explained her medical background, her procedure in some detail, and that the decision was an individual and personal one, as it always should be.

However, a one advantage of Jolie's story was the benefit that many women gained from learning about the BRCA gene mutations, the BRCA test, and what the outcomes can be for those who face the decision to have surgery.

While surgery is not the right option for everyone, studies have shown much higher rates of cancer prevention. Talk to your doctor. And keep the conversation going by joining the Drugs.com Support Groups for Breast Cancer and Ovarian Cancer. While these groups are never a substitute for the medical advice of your healthcare providers, here you can stay on top of the latest cancer news, ask questions of those in your similar situation, and voice your opinion, too.

Finished: Inherited Risk: The BRCA Gene Explained

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Sources

  • FDA Approves Lynparza (olaparib tablets) for Germline BRCA-Mutated Metastatic Breast Cancer. Drugs.com. Jan. 12, 2018. Accessed April 17, 2018 at https://www.drugs.com/newdrugs/fda-approves-lynparza-olaparib-germline-brca-mutated-metastatic-breast-cancer-4678.html
  • FDA Approves First Home Test for Three BRCA Breast Cancer Genes. Drugs.com. March 6, 2018. Accessed April 17, 2018 at https://www.drugs.com/news/fda-approves-first-home-test-three-brca-breast-cancer-genes-68913.html
  • Too Few High-Risk Women Tested for Breast Cancer Gene: Survey. Drugs.com. Feb 7, 2017. Accessed April 17, 2018 at https://www.drugs.com/news/few-risk-women-tested-breast-cancer-gene-survey-64398.html
  • National Cancer Institute (NCI). BRCA1 and BRCA2: Cancer Risk and Genetic Testing. Accessed April 17, 2018 at http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
  • BreastCancer.org. Genetic Testing Facilities and Cost. Last modified on June 23, 2016. Accessed April 17, 2018 at http://www.breastcancer.org/symptoms/testing/genetic/facility_cost
  • Final Update Summary: BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing. U.S. Preventive Services Task Force. July 2015. Accessed April 17, 2018 at https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/brca-related-cancer-risk-assessment-genetic-counseling-and-genetic-testing
  • Peshkin B, Isaacs C, et al. UpToDate. Patient information: Genetic testing for breast and ovarian cancer (Beyond the Basics). Accessed April 17, 2018 at https://www.uptodate.com/contents/genetic-testing-for-breast-and-ovarian-cancer-beyond-the-basics
  • Isaacs C, Peshkin B. UpToDate. Management of patients at high risk for breast and ovarian cancer. Last updated: Oct 11, 2016. Accessed April 17, 2018 at https://www.uptodate.com/contents/management-of-patients-at-high-risk-for-breast-and-ovarian-cancer

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