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BRCA1 Mutations and Triple-Negative Breast Cancer

Medically reviewed by Danielle Leonardo, M.D.
Written by Elizabeth Wescott
Posted on June 20, 2023

Have you or a family member received a positive test result for the breast cancer gene 1 (BRCA1) mutation along with a diagnosis of triple-negative breast cancer (TNBC)? People with a BRCA1 mutation have a higher risk of developing TNBC than other types of breast cancer. Among people with breast cancer who carry the BRCA1 gene mutation, 60 percent to 80 percent have TNBC.

This article will discuss how the BRCA1 mutation affects you and your family members’ cancer risk, as well as prognosis (outlook) and treatment options.

What Is BRCA1?

BRCA1 is a gene that helps to repair damaged DNA. Cancer develops when normal cells begin to behave and grow abnormally. If your BRCA1 gene is mutated, the cells lose their capacity to repair damaged DNA, and one way cells go haywire is through DNA damage.

The BRCA1 gene and its partner BRCA2 increase an individual’s risk for breast cancer. According to the National Cancer Institute, a woman with the BRCA1 mutation has about a 50 percent to 70 percent chance of developing breast cancer in their lifetime. This is significantly higher than the risk among women in the general population, which is only around 13 percent. Still, testing positive for BRCA1 doesn’t mean that a person will develop breast cancer.

Because this gene mutation can be passed down within families, if you or someone in your family has breast cancer or this mutation, your doctor may suggest genetic testing to determine who will need earlier screening or preventive treatments. Early detection of breast cancer through mammogram screenings is one of the best ways to prevent severe disease. Early-stage cancers typically respond much better to treatments.

Genetic Mutations and Your Cancer Risk

You may have heard that certain mutations in your DNA could increase your risk of developing certain types of cancer. Cancers, including breast cancers, are caused by gene mutations that encourage normal cells to grow out of control. Sometimes, these mutations are also passed down within families.

One example of this type of mutation is the BRCA1 mutation. This is an error in your DNA in a gene called BRCA1. An article in Frontiers in Oncology estimates that 10 percent of people with TNBC have germline mutations in BRCA1 or BRCA2. Germline means the mutation occurred in a sperm or egg cell and is present in every cell of the body.

A mutation in the BRCA1 gene can increase your risk of developing breast cancer or ovarian cancer. If you have a family history of breast cancer, your doctor may suggest you get genetic testing specifically for the BRCA1 gene.

If you’ve already been diagnosed with cancer, your doctor may also suggest you be tested to see if you have BRCA mutations. The test results can help doctors choose which treatments to recommend based on how the cancer cells are likely to grow.

BRCA1 and Triple-Negative Breast Cancer

Breast cancer can be divided into different subtypes based on which cells of the breast tissue are cancerous (e.g., ductal or lobular). Breast cancer cells may also be positive or negative for cell receptors that respond to hormones including estrogen and progesterone or the protein human epidermal growth factor 2 (HER2).

Breast cancers that have estrogen or progesterone receptors are called hormone receptor-positive cancers. Breast cancers that have HER2 receptors are known as HER2-positive cancers. Both of these types of breast cancer can be treated with targeted therapies specific to cells with those receptors.

If you have TNBC, your cancer doesn’t express any of the three — estrogen receptors, progesterone receptors, or HER2 protein — and is called triple-negative. Typically, these cancers are more difficult to treat because there isn’t an obvious target on the cancer cells. Many drugs may still work well for TNBC, but doctors have fewer options for treatment.

Doctors can treat TNBC through combinations of chemotherapies, immunotherapy, or radiation therapies to kill cancer cells. The consequence is these treatments can also kill healthy cells. Your doctor will help you weigh the benefits versus risks and recommend the treatment with the best chance of success.

Your Treatment Options and Prognosis

The type of breast cancer you have determines your treatment options. Even though TNBC is difficult to treat overall, there’s good news for people with a BRCA1 mutation. Some research shows that people with a BRCA1 mutation and TNBC actually have a better prognosis than people with TNBC but without a BRCA mutation.

Typically, if you have early-stage TNBC, doctors recommend surgery to remove your tumor and then undergo chemotherapy after surgery — called adjuvant therapy. Adjuvant therapy helps to ensure that cancer cells are completely removed from your body. People with the BRCA1 mutation and TNBC were found to be more responsive to adjuvant therapy, contributing to better outcomes for this group, including better overall survival.

Researchers have been testing different combinations of chemotherapy drugs with other drugs to find the best combination for people with TNBC and/or with the BRCA1 mutation. The U.S. Food and Drug Administration (FDA) has approved two drugs known as PARP inhibitors. This type of drug works by preventing cancer cells from trying to repair themselves after being damaged by chemotherapy.

Olaparib (Lynparza) is approved in people with TNBC that is early-stage or has metastasized (spread) in people with BRCA1 or BRCA2 mutations. Talazoparib (Talzenna) is also approved in people with BRCA1 mutations in TNBC that are either localized (have not spread) or metastatic.

When you discuss treatment options with your oncologist, you can ask what roles surgery, chemotherapy, and PARP inhibitors might have in your treatment plan.

Who Should Get Tested for BRCA1?

While certain genetic mutations can increase your risk of developing breast cancer, not all breast cancer is caused by the BRCA1 gene mutation. In fact, only around 5 percent to 10 percent of breast cancers are related to a mutation in the BRCA gene. According to the National Comprehensive Cancer Network, certain populations will benefit from genetic testing more than others. These include:

  • People diagnosed with TNBC
  • People who have been diagnosed with breast cancer or have a close family member who was diagnosed before the age of 50
  • Those of Ashkenazi Jewish heritage
  • People who have a family member with a BRCA1/2 gene mutation (germline BRCA mutation)
  • Males with breast cancer
  • Individuals with a family history of male breast cancer, ovarian, pancreatic, or high-risk prostate cancers

If you have a family history of breast cancer, it’s important to consult your oncologist if there is a need for genetic testing for you or your family members. If anyone in the family has a BRCA1 mutation, there is a risk of breast cancer for other family members.

If you haven’t been diagnosed with TNBC or are over age 60 with no family history of breast cancer, getting tested likely won’t provide your doctors with any useful information. Keep in mind that most breast cancers aren’t linked to the BRCA1/2 mutation.

Your doctor and oncology team can confirm whether genetic testing is helpful for your specific case. Early detection of TNBC is the best chance for remission (when signs and symptoms are reduced or disappear).

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 63,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Have you been diagnosed with TNBC and a BRCA1 mutation? How are you and your family handling this news? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Posted on June 20, 2023
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Danielle Leonardo, M.D. is a board-certified specialist in internal medicine and medical oncology from the Philippines and has been practicing medicine since 2014. Learn more about her here.
Elizabeth Wescott is currently completing her doctorate in immunology and cancer biology at Vanderbilt University, with a research focus on improving immunotherapy outcomes for patients with breast cancer. Learn more about her here.

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