Hereditary Breast Cancer: BRCA Mutations & Beyond

While there are several steps we can take to reduce cancer risk, some risk factors, like breast density and genetic makeup, are beyond our control. Although around one third of breast cancer cases are thought to arise from lifestyle factors like inactivity and alcohol consumption,[1] 5–10% are believed to result from hereditary gene mutations.[2] The most common of these mutations are in the BRCA1 and BRCA2 genes; however, mutations of other genes can also contribute to breast cancer development.

How do gene mutations affect cancer risk?

When functioning normally, the BRCA1 and BRCA2 genes help suppress tumors by producing proteins that mend damaged DNA. Mutations in these genes inhibit this function, which can facilitate abnormal cell growth and allow cancer to develop. As a result, people with BRCA1 or BRCA2 mutations are at a greater risk of breast, ovarian, and other cancers. In fact, women with these mutations face up to a 70% risk of developing breast cancer by age 80.[3] While other gene mutations can also contribute to breast cancer, these are less common and generally have a less dramatic impact on overall risk. Examples include mutations of the ATM, PALB2, TP53, CHEK2, PTEN, CDH1, and STK11 genes.

Should I be tested for gene mutations?

If you have a family or personal history of breast cancer, your doctor may recommend genetic counseling. A genetic counselor will review your family medical history and help determine whether genetic testing is advisable. If you decide to undergo testing, the counselor can also help you understand what the results mean for you and other family members. Testing is often advised for patients with

• Family members with known BRCA1 or BRCA2 mutations
• A strong family history of breast and/or ovarian cancer
• Ashkenazi or Eastern European Jewish ancestry and a moderate family history of breast and/or ovarian cancer
• Breast cancer diagnosis before age 45
• Triple negative breast cancer diagnosis before age 60
• Male breast cancer[4]

This is not an exhaustive list. If you have a known history of breast or ovarian cancer in your family or if you’ve been diagnosed with one of these cancers, talk to your doctor about whether genetic counseling could benefit you.

How can testing help?

If advised by your doctor, genetic testing can help protect your health and that of your close family members. If you don’t have cancer, knowing that you have a genetic mutation that predisposes you to the disease gives you a chance to take proactive steps early to reduce your cancer risk and increase your odds of living a long and healthy life. If you’ve been diagnosed with breast cancer, knowing whether it has a hereditary component can help guide your doctors toward the most effective known treatments. Additionally, identifying genetic mutations provides valuable information for other members of your family, since the parents, children, and siblings of those with a BRCA1 or BRCA2 mutation have a 50% chance of carrying the same mutation.[5]

What happens if my test is positive?

If you test positive for a mutation of the BRCA1 or BRCA2 gene, your genetic counselor will help you understand the implications of these results, and your doctor will discuss with you your options for controlling your breast cancer risk. These can include testing, medications, and surgery. For example,

• Patients with BRCA1 or BRCA2 gene mutations are advised to undergo annual breast MRI beginning at age 25 and annual mammography plus MRI beginning at age 30.[6]
• The estrogen-blocking drug Tamoxifen has been shown to reduce breast cancer risk in patients with BRCA2 mutations.
• Bilateral mastectomy has been shown to reduce breast cancer risk by 85% to 100% in women with BRCA mutations.[7]

Before deciding on a course of treatment, make sure you understand the potential risks and benefits of the medications or procedures you’re considering, including side effects, quality of life impacts, and success rates.

At Iowa Radiology, we take a personal approach to medicine, prioritizing excellent patient care. We provide a full range of breast imaging services, including 3-D mammography, breast MRI for high-risk patients, abbreviated breast MRI, and imaging-guided biopsy. Our skilled technologists are dedicated to providing compassionate care and helping patients remain as comfortable as possible throughout their time at our clinics. To learn more about breast cancer screening and prevention, subscribe to our blog.

Resources

[1] Lammert J, Grill S, Kiechle M. Modifiable Lifestyle Factors: Opportunities for (Hereditary) Breast Cancer Prevention—a Narrative Review. Breast Care (Basel). 2018;13(2):109–114. https://dx.doi.org/10.1159/000488995.

[2] American Cancer Society. Breast Cancer Risk Factors You Cannot Change. Cancer.org. Published December 16, 2021. Accessed September 18, 2023. https://www.cancer.org/cancer/types/breast-cancer/risk-and-prevention/breast-cancer-risk-factors-you-cannot-change.html.

[3] Ibid.

[4] Mayo Clinic. BRCA gene test for breast and ovarian cancer risk. MayoClinic.org. Published August 12, 2021. Accessed September 18, 2023. https://www.mayoclinic.org/tests-procedures/brca-gene-test/about/pac-20384815.

[5] Centers for Disease Control and Prevention. Genetic Testing for Hereditary Breast and Ovarian Cancer. CDC.gov. https://www.cdc.gov/genomics/disease/breast_ovarian_cancer/testing.htm. Published June 20, 2023. Accessed September 18, 2023.

[6] Elezaby M, Lees B, Maturen KE, et al. BRCA Mutation Carriers: Breast and Ovarian Cancer Screening Guidelines and Imaging Considerations. Radiology. 2019;291(3):554–569. https://doi.org/10.1148/radiol.2019181814.

[7] American College of Obstetricians and Gynecologists. BRCA1 and BRCA2 Mutations FAQ. https://www.acog.org/womens-health/faqs/brca1-and-brca2-mutations. Published December 2022. Accessed September 18, 2023.