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Is Triple-Negative Breast Cancer Genetic?

Medically reviewed by Maybell Nieves, M.D.
Written by Aminah Wali, Ph.D.
Posted on January 18, 2024

Many factors influence your risk of developing triple-negative breast cancer (TNBC), and some are out of your control. Research has shown that some aspects of a person’s background can make them more likely to have TNBC. These factors may include a family history of breast cancer, genetics, and race or ethnicity.

TNBC is a fast-growing type of breast cancer that tends to metastasize (spread). It lacks the proteins known as estrogen receptors and progesterone receptors and has low levels of another protein, human epidermal growth factor receptor 2 (HER2). Since these three proteins are missing from cancer cells in TNBC, the disease is more difficult to treat and more likely to cause death compared with other breast cancer subtypes.

TNBC can run in families and is more common in certain populations. This article will cover different inherited risk factors that can increase the chance of getting TNBC. By learning whether your cancer may have genetic factors, you can better understand your family’s risk of developing the disease.

Understanding Genetic Mutations and Triple-Negative Breast Cancer

Genes are sections of your DNA that tell cells how to work and what proteins to make. Abnormal variations of genes are called mutations. Genetic mutations may either be inherited from a biological parent or develop over time. Acquired mutations may result from exposure to radiation or certain chemicals, among other environmental factors.

African American women have a higher risk of TNBC than any other racial or ethnic group in the United States.

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Whether they’re inherited or acquired, mutations to genes that control functions like growth or DNA repair may cause cells to become cancerous. Only about 10 percent of breast cancers are known to be linked to inherited abnormal genes. Most breast cancers are believed to result from acquired mutations.

Researchers have linked different gene mutations with TNBC.

BRCA1 and BRCA2 Mutations

Mutations in the BRCA1 gene are a major genetic cause of TNBC. Although BRCA1 is linked to other forms of breast cancer as well, more than half of BRCA1-mutated cancers are the TNBC subtype. Mutations in a similar gene, BRCA2, are also linked to TNBC.

In normal breast cancer cells, both BRCA1 and BRCA2 play important roles in fixing damaged areas of DNA. When these genes are mutated, the repair process can’t be done properly, and cancer can develop. People with these mutations also tend to get cancer at a younger age compared to those without mutations.

If you’re not sure whether you have a BRCA1 or BRCA2 mutation, you can get tested to check. The National Comprehensive Cancer Network recommends testing for people with a known family history of cancer or BRCA gene mutations. If your test comes back positive, that means you, your children, or other family members may be at risk of breast cancer. Knowing your mutation status is also helpful when doctors are weighing treatment options, because certain drugs may work better in people with BRCA gene mutations.

Other Gene Changes

While the link between BRCA gene mutations and breast cancer is well known, research to better understand the genetic causes of TNBC is still ongoing. A 2018 study compared dozens of genes in people with TNBC to those without TNBC. The researchers found that — in addition to BRCA1 and BRCA2 — people with TNBC were more likely to have mutations in the following genes:

  • PALB2
  • RAD51D
  • BARD1

The findings provide additional clues about the genetic causes of TNBC. Testing for these newer gene mutations — not just BRCA1 and BRCA2 — during breast cancer screening may help assess who has a high risk of getting TNBC and even help oncologists consider prognosis or treatment options.

Inherited BRCA gene mutations are a common cause of TNBC in people of Ashkenazi Jewish descent.

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Read more about treatment options for TNBC.

Recognizing Racial and Ethnic Differences in Triple-Negative Breast Cancer

TNBC is more common in certain racial and ethnic groups. Understanding which groups are at an increased risk of TNBC may help improve the chances of diagnosing the disease early.

TNBC Risk Is Highest in African Americans

African American women have the highest risk of TNBC compared with any other racial or ethnic group in the United States, according to a study in the journal Cancers. In a 2020 review article in Frontiers in Public Health, the authors reported that, compared with white women, African American women are more likely to:

  • Be diagnosed with TNBC
  • Be diagnosed at a younger age
  • Die from the disease

It’s not well understood why TNBC leads to worse outcomes in African Americans, but research offers some clues. Although African American women aren’t more likely to have BRCA gene mutations, they do have higher rates of other types of gene mutations compared with European American women. Some of these genes have been linked to TNBC in African Americans.

Additionally, although many studies are done in the U.S. population, women with African ancestry in other parts of the world also have higher rates of TNBC. While the complete nature of these genetic links still isn’t clear, it’s possible that inherited mutations in certain populations may increase the risk of TNBC.

Hispanic People Tend To Be Diagnosed at a Young Age

Racial and ethnic disparities in TNBC may also affect Hispanic women. Compared with non-Hispanic white women, Hispanic women tend to be diagnosed with TNBC more often and, according to a 2022 study in Frontiers in Public Health, usually at a younger age. Hispanic women may also have more advanced disease and more aggressive tumors at the time of breast cancer diagnosis.

Hispanic women tend to be diagnosed with TNBC more often and usually at a younger age compared with white women.

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It’s not clear what biological risk factors might increase TNBC risk in the Hispanic population. This is partly because Hispanic women are underrepresented in studies looking at breast cancer subtypes. There’s still a need for more research to better understand the risk of TNBC in the Hispanic population.

BRCA Mutations Occur Most Often in Ashkenazi Jewish People

TNBC also occurs frequently among women of Ashkenazi Jewish descent. In this population, the risk of TNBC is strongly linked to BRCA1 and BRCA2 mutations. In one study, nearly 40 percent of 64 Ashkenazi Jewish women with TNBC had BRCA gene mutations. This percentage was even higher for women under 50 — more than half carried one of these mutations.

Another study looked only at people with BRCA1 mutations to understand who usually gets TNBC. The researchers found that Ashkenazi Jewish women were much more likely to have TNBC compared with other ethnic or religious groups. These findings show that inherited BRCA gene mutations can often cause TNBC in people of Ashkenazi Jewish descent.

Figuring Out Your Family’s Risk

If you or a loved one has been diagnosed with TNBC, you may wonder if your family has a history of TNBC or whether other relatives have a higher risk of developing it. Mention your concerns to your doctor — they can help you figure out the next steps. They may recommend getting genetic counseling to better understand your family history or being tested for BRCA gene mutations. A positive test can mean your disease has a genetic link, so it may be a good idea for your children or other family members to get tested as well.

If you belong to a racial or ethnic group that may be at higher risk of TNBC, know that a lot remains unknown about what causes TNBC in certain populations. More research is needed to understand the causes of TNBC and improve treatment and outcomes for people who are at risk. Meanwhile, your doctor can help you best understand your risk factors and how to address them.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 67,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Does triple-negative breast cancer run in your family? Do you know if you have any genetic risk factors? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

References
  1. Triple-Negative Breast Cancer — American Cancer Society
  2. Gene Changes and Cancer — American Cancer Society
  3. What Causes Breast Cancer? — American Cancer Society
  4. Family History of Breast Cancer in First-Degree Relatives and Triple-Negative Breast Cancer Risk — Breast Cancer Research and Treatment
  5. Gene Changes and Cancer — American Cancer Society
  6. ASCO: Studies Show Advances in Treatment and Understanding of BRCA-Associated and Triple-Negative Breast Cancer — The University of Texas MD Anderson Cancer Center
  7. BRCA Gene Mutations: Cancer Risk and Genetic Testing — National Cancer Institute
  8. Treatment of Triple-Negative Breast Cancer — American Cancer Society
  9. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing — Journal of the National Cancer Institute
  10. Triple Negative Breast Cancer Risk Factors — Moffitt Cancer Center
  11. Racial Disparity and Triple-Negative Breast Cancer in African-American Women: A Multifaceted Affair Between Obesity, Biology, and Socioeconomic Determinants — Cancers
  12. Racial Disparities in Triple Negative Breast Cancer: A Review of the Role of Biologic and Non-Biologic Factors — Frontiers in Public Health
  13. Racial and Regional Disparities of Triple Negative Breast Cancer Incidence Rates in the United States: An Analysis of 2011-2019 NPCR and SEER Incidence Data — Frontiers in Public Health
  14. Ethnic Disparities in Breast Tumor Phenotypic Subtypes in Hispanic and Non-Hispanic White Women — Journal of Women’s Health
  15. Relative Contributions of BRCA1 and BRCA2 Mutations to ‘Triple-Negative’ Breast Cancer in Ashkenazi Women — Breast Cancer Research and Treatment
  16. Characteristics of Triple-Negative Breast Cancer in Patients With a BRCA1 Mutation: Results From a Population-Based Study of Young Women — Journal of Clinical Oncology
  17. Triple Negative Breast Cancer: An Overview — Hereditary Genetics Journal
    Posted on January 18, 2024
    All updates must be accompanied by text or a picture.

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    Maybell Nieves, M.D. graduated from Central University of Venezuela, where she completed medical school and general surgery training. Learn more about her here
    Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here

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