BRCA1/BRCA2 Genetic Testing: Reducing Breast and Ovarian Cancer Risk

, Fact-checked by: Dr. Heena A., PhD / 【┘】Last updated on January 17, 2024
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Breast and ovarian cancer significantly impact women’s health around the globe. As per World Health Organization data, in 2020, breast cancer affected about 2.3 million women and led to the death of 604,000, while ovarian cancer impacted 295,000 women and caused 185,000 deaths.

The risk of these cancers can stem from various factors, including age, lifestyle, and environmental influences. Still, the danger is rooted in the woman’s genetic blueprint in some cases.

In this article, we delve into how the BRCA1 and BRCA2 genes operate, the role of mutations in these genes, who should think about BRCA genetic testing, what the test results mean, and how one can minimize the risk of cancer with a harmful mutation.

Quick Overview:

BRCA1 and BRCA2 genes in normal situations help prevent cancer by repairing DNA damage and controlling abnormal cell growth.

However, if a person inherits certain changes or mutations in these genes, they may not work as they should, increasing the risk of cancers such as breast and ovarian.

Women with BRCA1 or BRCA2 mutations are more likely (is some cases up to 72% high) to develop breast cancer than those without.

BRCA genetic testing becomes crucial if somebody is already affected by cancer in the family. By testing for the BRCA gene, we can find out if someone has inherited these mutations, helping them make informed healthcare decisions.

For instance, some people may opt for more regular screening tests like mammograms, while others may decide on preventive surgery to lower cancer risk.

Understanding BRCA1/BRCA2 Genes

BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes responsible for producing proteins that repair DNA damage. DNA, which carries our genetic information, can sometimes get damaged due to factors like radiation, chemicals, and viruses, leading to changes in the DNA sequence that can affect how genes work.

When these genes are impacted, it can disrupt the balance of cell growth and death, causing uncontrolled cell division and, potentially, tumor growth.

BRCA1 and BRCA2, often referred to as tumor suppressor genes, aid in preventing cancer by rectifying DNA damage and putting a stop to abnormal cell growth. They achieve this by interacting with other proteins and enzymes involved in the DNA repair process.

But, if a person inherits mutations or changes in the BRCA1 or BRCA2 that make them ineffective or non-functional, these genes cannot do their job correctly.

These mutations, which can be inherited from either parent, exist in all cells of the body from birth. While people with a harmful variant in the BRCA gene have a heightened risk of developing breast, ovarian, and other cancers, not everyone who inherits a harmful variant will get cancer. This is because they still have one normal copy of the gene from the other parent that can counterbalance the defective one.

However, cancer can occur when a second mutation impacts the normal gene copy in some body cells during their lifetime. This second mutation, which is not inherited, can result from environmental factors or random errors during cell division.

Several factors can affect the risk of developing cancer due to BRCA1 or BRCA2 mutations, such as the mutation’s type and location, family cancer history, and exposure to other risk factors. Hundreds of mutations have been identified in these genes; some are more harmful than others.

Certain populations, like people of Ashkenazi Jewish descent, have a higher frequency of specific BRCA1 and BRCA2 mutations.

BRCA1/BRCA2 Genetic Testing: Procedure and Interpretation

The test for the BRCA gene, which is a blood or saliva test, can find these mutations. This BRCA genetic testing can help people make decisions about their health.

Who should get tested for BRCA mutations

If you or someone in your family has had breast or ovarian cancer, getting tested for breast cancer genes, specifically the BRCA1/BRCA2 mutations, might be a good idea.

You should consider testing for the BRCA gene, especially if you fall into any of these categories:

  • You had breast cancer before turning 50.
  • You’ve had cancer in both breasts or different types of cancer.
  • A male in your family has had breast cancer.
  • A family member has a known BRCA1/BRCA2 mutation.
  • You have Ashkenazi Jewish or Eastern European roots, and there’s a history of breast or ovarian cancer in your family.

Doctors may also test tumor samples from people who already have cancer. This helps them determine if these people are good candidates for specific treatments.

How the genetic test for BRCA genes is done

When you go in for a BRCA genetic test, doctors will usually take a sample of your blood or saliva. They send this sample to a lab where scientists study your DNA to check for mutations in the BRCA1 and BRCA2 genes.

The test could check several genes related to cancer at once or focus on specific mutations more common in certain ethnic groups. The results of your genetic test for BRCA usually come back in a few days.

What the test results mean

The genetic test for BRCA can give three types of results:

  • Positive: This means the test found a harmful mutation in your BRCA1 or BRCA2 genes. A positive result doesn’t mean you have cancer or will surely get it. But, it does mean you’re at a higher risk than most people. If you have a positive result, this also means your blood relatives might share your mutation and risk.
  • Negative: This means the test didn’t find any harmful BRCA1 or BRCA2 mutations. This doesn’t mean you have zero risk of getting cancer, but your risk isn’t higher because of these genes. A negative result might also mean the test missed a different mutation or you have a mutation in a different gene linked to cancer risk.
  • Uncertain: This means the test found a variant of unknown significance (VUS) in your BRCA1 or BRCA2 genes. A VUS is a change in these genes that doctors aren’t sure is harmful or not. More research is needed to understand how these variants might affect cancer risk.

The odds and risk percentages linked to BRCA1/BRCA2 mutations

How much having a BRCA1/BRCA2 mutation raises your cancer risk depends on several factors, such as the type and location of the mutation, the type and age of onset of cancer, and other genetic and environmental factors. But, scientists have found some rough estimates based on studies:

  • Women with a harmful BRCA1 mutation have around a 72% chance of getting breast cancer and about a 44% chance of getting ovarian cancer by the age of 80.
  • Women with a harmful BRCA2 mutation have around a 69% chance of getting breast cancer and about a 17% chance of getting ovarian cancer by the age of 80.
  • Men with a harmful BRCA1 mutation have around a 1% chance of getting breast cancer and about a 4% chance of getting prostate cancer by age 80.
  • Men with a harmful BRCA2 mutation have around a 7% chance of getting breast cancer and about a 15% chance of getting prostate cancer by age 80.
  • People with a harmful mutation in either BRCA gene also have a higher risk of getting other types of cancers, like pancreatic cancer and melanoma.

What Positive Test Results Mean for You

If your test for the BRCA gene is positive, this not only affects you, but also your blood relatives. It can also affect your mental and emotional well-being, and you might need help and guidance to cope.

Immediate effects

If a person gets a positive BRCA genetic test result, they’ll face several decisions and challenges, like:

  • Deciding whether to share their test result with family, friends, and doctors.
  • Deciding whether to get screened for cancer more often, like getting mammograms, breast MRIs, pelvic ultrasounds, and CA-125 blood tests.
  • Considering ways to prevent cancer, like having surgery to remove your breasts and/or ovaries, taking drugs that lower your cancer risk, or changing your lifestyle.
  • Considering whether to take part in clinical trials or research studies that might offer new treatments or insights into cancer risk and prevention.
  • Thinking about getting legal or financial advice on issues like insurance coverage, discrimination, and privacy.

What it means for blood relatives

A positive test result for the breast cancer gene also means your blood relatives – like parents, siblings, children, cousins, aunts, and uncles might have inherited the same mutation and have a higher cancer risk.

So, they could also benefit from genetic counseling and testing to understand their own risk and ways to prevent cancer.

How a positive test result can affect you psychologically

Getting a positive result from a BRCA genetic test can have a big impact on your mental health and on the mental health of your family members. You might feel a range of emotions like shock, fear, anger, guilt, sadness, anxiety, or relief.

You might also see changes in how you see yourself, your relationships, and your plans for the future. Some people cope well with the test result and its effects, while others might deal with stress, depression, or feeling isolated.

How a positive test result affects you can change over time and depends on things like your age, sex, family history, personal history, social support, coping skills, and personality.

The importance of getting genetic counseling if your test results are positive

Genetic counseling is a key service that can help if your BRCA genetic test results are positive. Genetic counselors are health professionals trained in medical genetics and counseling.

They can explain your test results, the odds and risk percentages linked to the mutations, the pros, and cons of different prevention options, what this means for your family, and where to find resources and support groups.

They can also help you talk about your test results with your relatives and doctors. You’re usually offered genetic counseling before and after genetic testing so that you’re well-informed and supported throughout the process.

Preventative Measures and Treatment Options for BRCA1/BRCA2 Mutation Carriers

If a woman carries a harmful change or mutation in her BRCA1 or BRCA2 gene, also known as the breast cancer gene, she has a much higher chance of getting breast and ovarian cancer, along with other types of cancer.

Because of this, it’s crucial for these women to think about different ways they can lower their chances of getting cancer or find it early if it does develop.

These ways include:

  • Regular screenings: Frequent check-ups and tests that can help spot cancer early, when it’s easiest to treat
  • Prophylactic surgeries: Operations done before cancer develops to remove the body parts most likely to get cancer, like the breasts and ovaries
  • Chemoprevention: Medicines that can lower the chances of getting certain cancers by blocking or messing with the effects of hormones or other things that help cancer grow
  • Changing lifestyle habits: Making changes in diet, exercise, smoking, alcohol use, and other factors that can impact cancer risk

Choosing between these risk-reducing strategies depends on many things. For example, the kind and seriousness of the BRCA gene mutation, personal and family history of cancer, age, plans to have children, personal choices and values.

So, it’s advised that women who test positive for BRCA1 or BRCA2 mutations talk to a genetic counselor and a team of healthcare providers to understand the pros and cons of each option and make informed decisions.

Regular screenings and check-ups

Regular screenings aim to find cancer at an early stage when it can be more easily treated. However, these screenings can’t prevent cancer. Here are some screenings women who carry BRCA1 or BRCA2 mutations should consider:

  • Breast cancer screening: Current guidelines suggest that women should have a breast MRI (magnetic resonance imaging) every year starting as early as 25 years old, and mammography or digital breast tomosynthesis (DBT) should be added to this yearly testing starting at 30 years old. The breast MRI is more effective at finding breast cancers in women with dense breasts or BRCA mutations, but it can sometimes give false-positive results, which might lead to unnecessary biopsies or worry. Mammography and DBT use low-dose x-rays to create pictures of the breast tissue. They can find some breast cancers that are not seen on the MRI, such as calcifications that may indicate ductal carcinoma in situ (DCIS), a non-invasive type of breast cancer. So, using both MRI and mammography or DBT may provide the best chance of finding breast cancer early in women with BRCA mutations.
  • Ovarian cancer screening: For women who haven’t had prophylactic bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes), a transvaginal ultrasound (TVUS) combined with serum CA-125 (a blood test) may be considered for ovarian cancer screening starting at age 30–35 years. TVUS uses sound waves to create pictures of the ovaries and other pelvic organs. It can find some ovarian tumors but can’t tell the difference between cancerous and non-cancerous ones. CA-125 is a protein that some ovarian cancers and other conditions produce. It can be elevated in women with ovarian cancer, but it can also be normal in some cases or elevated in non-cancerous conditions. Therefore, TVUS and CA-125 are not very accurate for ovarian cancer screening and may give false results.
  • Other cancer screenings: Women with BRCA mutations may also have a higher risk of developing other types of cancer, such as pancreatic cancer, melanoma (skin cancer), prostate cancer (in men), and male breast cancer (in men). Therefore, they might benefit from additional screenings for these cancers depending on their personal and family history, genetic test results, and other risk factors. However, how effective these screenings are in reducing cancer deaths in BRCA mutation carriers isn’t well established and may vary depending on the individual situation.

Prophylactic surgeries: removing both breasts and ovaries

Prophylactic surgeries are preventive operations that remove the body parts most likely to get cancer in women with BRCA mutations. These surgeries can greatly lower the risk of developing breast and ovarian cancer, and the risk of dying from these cancers. But they can also have potential complications, side effects, and psychological impacts that need to be considered.

Here are some of the prophylactic surgeries for women who carry BRCA1 or BRCA2 mutations:

  • Bilateral mastectomy: This is the surgical removal of both breasts. It can lower the chance of getting breast cancer by about 95% in women with BRCA mutations. It can also lower the risk of dying from breast cancer by about 50% in women who have already been diagnosed with breast cancer and have a BRCA mutation. However, this operation doesn’t entirely remove the risk of breast cancer, as some breast tissue might remain after the surgery. Also, it may cause physical complications like infection, bleeding, pain, scarring, loss of sensation, and lymphedema (swelling of the arm due to fluid buildup). It can also affect a woman’s body image, sexual function, ability to have children and quality of life. So, women who decide to have a bilateral mastectomy should be informed about the benefits and risks of the surgery, as well as the options for breast reconstruction or prosthesis.
  • Salpingo-oophorectomy: This is the surgical removal of both ovaries and fallopian tubes. It can reduce the risk of developing ovarian cancer by about 80% and breast cancer by about 50% in women with BRCA mutations. It can also reduce the risk of dying from ovarian cancer by about 80% and breast cancer by about 20% in women who have already been diagnosed with breast cancer and have a BRCA mutation. However, this operation also has potential drawbacks, like surgical complications, early menopause, loss of fertility, increased risk of osteoporosis (bone loss) and cardiovascular disease (heart disease and stroke), and reduced sexual function and well-being. So, women who decide to have a salpingo-oophorectomy should be informed about the benefits and risks of the surgery, as well as the options for hormone replacement therapy (HRT) or non-hormonal treatments for menopausal symptoms.

Chemoprevention: medicines that can reduce risk

Chemoprevention involves using medicines that can lower the chances of getting certain cancers by blocking or messing with the effects of hormones or other things that help cancer grow. Here are some of the chemoprevention options for women who carry BRCA1 or BRCA2 mutations:

  • Tamoxifen: This is a drug that blocks the effect of estrogen on breast cells. It can reduce the chance of getting estrogen receptor-positive (ER+) breast cancer by about 50% in women with BRCA2 mutations. However, it doesn’t change the risk of getting estrogen receptor-negative (ER-) breast cancer, which is more common in women with BRCA1 mutations. Also, tamoxifen might increase the chance of getting endometrial cancer (cancer of the lining of the uterus), blood clots, stroke, cataracts (clouding of the lens of the eye), and hot flashes. So, women who choose to take tamoxifen should be checked for these potential side effects and weigh the benefits and risks of the drug with their health care providers.
  • Raloxifene: This is another drug that blocks the effect of estrogen on breast cells. It can reduce the risk of getting ER+ breast cancer by about 38% in postmenopausal women at high risk for breast cancer. However, it’s not clear whether it’s effective in reducing breast cancer risk in women with BRCA mutations. Like tamoxifen, raloxifene may also increase the risk.

The Future of BRCA1/BRCA2 Genetic Testing

Over time, this kind of testing has become an incredibly helpful tool for assessing the risk in both individuals and families. As technology gets better and better, there are new methods that could make these BRCA tests more accurate, more widely available, and more useful.

One of the ways BRCA genetic testing is evolving is through the use of wider gene panels. These technologies can check for changes in many genes simultaneously, including genes other than the BRCA genes that might also make cancer more likely. For example, some panels can look at more than 20 different genes linked to hereditary breast and ovarian cancer syndrome.

Another big change is how we use personalized medicine for treating cancer. Personalized medicine is about customizing medical care to fit the unique characteristics of each patient, like their genetic makeup, lifestyle, and environment.

If you’ve inherited a harmful variant in the BRCA1 or BRCA2 gene, personalized medicine could offer more effective, tailored treatments that exploit the specific weaknesses of your cancer cells. For example, drugs called PARP inhibitors can stop cancer cells with BRCA mutations from repairing DNA damage, which causes them to die.

With these new technologies and improvements, the potential to prevent, diagnose, and treat cancer in people who’ve inherited a harmful variant in the BRCA1 or BRCA2 genes is increasing.

Final Words

Testing for the breast cancer gene (BRCA1 and BRCA2) is vital for understanding the risk of breast and ovarian cancer in individuals and families with a history of these cancers.

If you inherit a harmful variant in one of these genes, your chances of developing breast and ovarian cancer significantly increase compared to the general population. You also face a higher risk of other cancers, like prostate, pancreatic, and melanoma.

Understanding your genetic risk can help you make smarter decisions about your healthcare and preventive options. If you’ve inherited a harmful variant in the BRCA1 or BRCA2 gene, you can reduce your risk of cancer by getting regular screening tests, taking preventive medicines, or undergoing preventive surgeries.

That said, not everyone needs a test for the BRCA gene. It’s mainly for people with a strong personal or family history of breast or ovarian cancer, or those from certain ethnic groups with a higher number of founder mutations.

If you’re considering BRCA genetic testing, you should discuss it with healthcare professionals who can provide genetic counseling before and after the test.

This counseling can help you understand the pros and cons of BRCA genetic testing, help you interpret your test results, and support you in dealing with the emotional impact of learning your genetic status.

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