What Is Triple-Negative Breast Cancer?

Triple-negative breast cancer is an aggressive type of breast cancer with its own symptoms and treatments.

triple-negative-breast-cancer
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Breast cancer occurs when cells in the breast tissue change and grow uncontrollably, according to the National Library of Medicine MedlinePlus resource. It's the second most common cancer in cisgender women in the US, per the American Cancer Society (ACS).

Triple-negative breast cancer (TNBC) is more aggressive and harder to treat than other breast cancers. About 10–15% of all breast cancer cases in the US are triple-negative, per the ACS. Its name refers to its cancer cell characteristics. Healthcare providers check for three receptors on the cancer cell.

Two are for the hormones estrogen and progesterone, and the other is a protein called human epidermal growth factor (HER2), according to the Centers for Disease Control and Prevention (CDC). When one of the two hormones, estrogen or progesterone, attaches to the corresponding receptor on a breast cancer cell, it promotes cancer growth, per the ACS. Similarly, HER2 in breast cancer cells speeds up their growth, per the ACS In TNBC, all three components are missing—neither estrogen nor progesterone helps it grow, and there isn't much (or any) HER2 involved.

Fewer treatment options exist for TNBC, and it's more likely to return after treatment, leading to lower survival rates, according to 2012–2018 data from the National Cancer Institute (NCI). That said, treatments have advanced rapidly over the years.

Causes

Triple-negative breast cancer is the least understood type of breast cancer, per a February 2015 study published in the journal Gene.

Breast cancer in general occurs because of changes in your DNA (genetic material). These changes can be inherited or occur because of environmental or lifestyle factors. Researchers have found many risk factors for breast cancer, such as older age and drinking alcohol, per MedlinePlus. But in most cases the cause is unknown.

However, a September 2015 review published in Archives of Gynecology and Obstetrics noted about 60–80% of breast tumors in people with a BRCA1 mutation were cases of TNBC. BRCA1 and BRCA2 mutations are associated with a higher risk of breast cancer in general. Genetic testing can determine if you have a BRCA mutation.

Risk Factors

Compared to other breast cancers, TNBC is more likely to occur in premenopausal people under 40 years old and those who are non-Hispanic Black or Hispanic, per the September 2015 review. In the US, the rate of TNBC in non-Hispanic Black cisgender women is about double the rate of other racial and ethnic groups, according to 2019–2020 data from the ACS.

Risks for breast cancer also include, per MedlinePlus and the NCI:

  • Genetics
  • Dense breast tissue
  • Prior radiation therapy to the breast or chest
  • Obesity
  • Alcohol consumption
  • Some aspects of your reproductive history, such as getting your period at an earlier age or giving birth to your first child at an older age (older than 30 years old, per the NCI)

Despite common perception, not enough evidence exists to prove the following factors contribute to breast cancer risk:

Symptoms

Triple-negative breast cancer symptoms are the same as those of other common breast cancers. And they overlap with other less serious medical conditions, such as mastitis (an infection common in breastfeeding people) or breast cysts (non-cancerous lumps filled with fluid), per the ACS.

If you experience the following breast cancer symptoms, speak to your healthcare provider, who can help determine the cause of the issue:

  • New lump or thickening in the breast or armpit: This is the most common symptom of breast cancer but is not always a sign that you have the disease. Cancerous lumps are more likely to be painless and hard with irregular edges, but not necessarily, per the ACS.
  • Changes in the way the breast looks: These can include swelling, skin dimpling (when the skin begins to look like an orange), a nipple that turns inward, and scaly or red skin, per MedlinePlus.
  • Nipple discharge that's not breast milk: Instead of milk, the discharge may be bloody, happen suddenly, and only in one breast, per MedlinePlus.
  • Pain in the breast or nipple

Non-cancerous breast conditions can also cause these, but if you see or feel changes in your breasts, make sure to speak to your healthcare provider.

Diagnosis

As with all types of breast cancer, early detection and treatment are crucial. If your healthcare provider suspects you may have breast cancer, they can use the following tools for further evaluation, per MedlinePlus:

  • Physical exam: A clinical breast exam involves a healthcare provider checking the breasts for any signs of cancer, such as dimpling or lumps.
  • Discussion of personal and family medical history: About 5–10% of all cancers develop because of inherited genetic mutations, per the NCI. Sometimes, a shared environment or similar lifestyles of family members can also heighten cancer risk.
  • Imaging tests: These can include a mammogram, breast ultrasound, or breast MRI.
  • Breast biopsy: The procedure removes your cells or tissues for examination by a specialist.
  • Blood tests: Your provider may measure multiple substances in the blood, such as electrolytes, fats, proteins, glucose (blood sugar), and enzymes, per MedlinePlus.

These tests can determine if you have breast cancer, but they can't show its type. After diagnosis, your healthcare provider will order more tests to determine the type and stage of cancer.

To find out if the cancer is triple-negative, you'll need tests to check the cancer cells for HER2 and estrogen and progesterone receptors. Your provider may also order genetic tests.

Treatment

As of March 2022, there were fewer treatments for TNBC than other types of breast cancers, per the ACS. That is partially because hormone therapy and targeted HER2 drugs don't work on a disease that is hormone receptor-negative and doesn't have much or any HER2.

Common TNBC treatments include:

  • Chemotherapy: A common choice for people with TNBC at all stages, it's a systemic (whole-body) drug-based treatment that can help stop cancer cells' growth. Chemo tends to work well for people with TNBC at first, but the cancer can return and does so more often than for other types of breast cancer, according to the ACS. Side effects include hair loss, nausea, and tiredness, per the CDC.
  • Surgery: For TNBC in stages 1-3, people may get surgery before or after chemotherapy. The two types of surgery are lumpectomy—when just the lump is removed from the breast—and mastectomy—removing the whole breast and nearby lymph nodes (structures in the body's immune system), per the CDC. A surgeon may be able to rebuild the breast after a mastectomy during the same surgery.
  • Radiation therapy: This may follow surgery if the tumor is large or cancer has spread to the nearby lymph nodes. This type of therapy uses high-energy rays or particles to destroy cancer cells at specific locations.

Stage 4 Triple-Negative Breast Cancer

If TNBC spreads to distant organs, it becomes stage 4, or metastatic, breast cancer. Breast cancers in this stage are not curable, but they can be treated to prolong lives and reduce symptoms. Treatment for stage 4 TNBC includes:

  • Chemotherapy
  • Drug therapies like immunotherapy or targeted therapy
  • Surgery
  • Radiation therapy

Recurrent Triple-Negative Breast Cancer

Recurrent TNBC (TNBC that has come back) that hasn't spread can be treated with chemotherapy in combination with immunotherapy. Recurrent TNBC that has spread can also be treated with a medication called Trodelvy (govitecan), which the Federal Food & Drug Administration (FDA) approved in 2020.

Trodelvy is a targeted drug therapy—meaning it attacks specific cancer cells in the body—and it's the first targeted therapy for TNBC, per the FDA. You can only take Trodelvy after you've tried at least two other cancer therapies. The medication comes with side effects such as severe diarrhea and low white blood cell counts. White blood cells are part of the body's immune system.

Additional clinical trials for TNBC treatments are ongoing. Participating in them can give you access to new drugs or therapies, per the ACS.

Prevention

There's no sure way to prevent TNBC or any type of breast cancer, but some lifestyle interventions may reduce your risk. These include, per MedlinePlus:

  • Maintaining a healthy weight: Obesity is a risk factor for breast cancer, including TNBC, per a paper published in the January–February 2021 issue of the Cancer Journal.
  • Reducing alcohol consumption: Drinking any type of alcohol can raise your risk for several types of cancer, including breast and liver, per the CDC. This risk increases the more you drink.
  • Getting regular exercise: Not being physically active is a risk factor for breast cancer in women, per the CDC.

Additionally, research published in January 2017 in the journal Breast Cancer Research showed that breastfeeding for at least a year reduces TNBC risk, especially for African American cisgender women aged 20–44.

Getting regular screenings if you are at a higher risk is important to improve your treatment outlook. And no matter the risk, pay attention to any changes in your breasts. If you feel anything is off, contact a healthcare provider right away.

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