Woman with short black hair standing in a bra gives herself a breast exam in the mirror.

What Is Triple-Negative Breast Cancer?

Triple-negative breast cancer is a fast-growing cancer that is more likely to return than other breast cancers.

Breast cancer occurs when cells in the breast tissue change and grow out of control. Breast cancer is the second most common cancer among women in the United States.

Triple-negative breast cancer (TNBC) is more aggressive and challenging to treat than other breast cancers. The name refers to its cancer cell characteristics. Healthcare providers check for three receptors on the cancer cell. 

Two are for estrogen and progesterone hormones; the other is a human epidermal growth factor (HER2) protein. When estrogen or progesterone attaches to the corresponding receptor on a breast cancer cell, it promotes cancer cell growth.

HER2 in breast cancer cells speeds up their growth. In TNBC, all three components are missing. Neither estrogen nor progesterone helps cancer cells grow, and there is little to no HER2 involved.

About 10% to 15% of all breast cancers in the United States are triple-negative. Few treatment options exist for TNBC, and it's more likely to return after treatment, leading to lower survival rates than other breast cancers. That said, treatments have advanced rapidly over the years.

Types of Triple-Negative Breast Cancer

Research has identified different types of TNBC. Cases of TNBC may vary on a molecular level, meaning that different cells, genes, and hormone receptors are involved. Although, there are no standard guidelines for diagnosing types of TNBC.

Basal-Like

These cancer cells resemble the cells that comprise the outermost layer of the breast milk ducts.  

Basal-like cancer cells may be immune-activated or immune-suppressed. Basal-like immune-activated cancer cells may respond better to treatments than immune-suppressed ones.

Luminal Androgen Receptor

This type of TNBC involves androgen receptors and luminal genes. Androgen receptors are proteins that bind the male hormone androgen. Androgen receptors are found in some breast cancer cells, causing them to grow.

Mesenchymal

This type of TNBC involves stem cells that become connective tissue, blood vessels, and lymphatic tissue. 

Connective tissues protect and support your tissues and organs. Lymphatic tissue creates and stores white blood cells, which fight germs that cause illness.

Triple-Negative Breast Cancer Symptoms 

TNBC symptoms are the same as those of other breast cancers. 

Consult a healthcare provider right away if you notice TNBC symptoms like:

  • Changes in the way the breast looks: These can include swelling, skin dimpling (i.e., the skin looks like an orange peel), a nipple that turns inward, and scaly or red skin.
  • New lump or thickening in the breast or armpit: This is one of the most common symptoms of breast cancer. A new lump is not always a sign that you have the disease. Cancerous lumps are more likely to be painless and hard with irregular edges than benign ones, but not always.
  • Nipple discharge that's not breast milk: The discharge may be bloody, happen suddenly, and only occur in one breast.
  • Pain: You may feel pain in any part of your breast or the nipple.

TNBC symptoms may overlap with other, less severe health conditions, such as mastitis or breast cysts. Mastitis is an infection common in breastfeeding people. Breast cysts are non-cancerous lumps filled with fluid. Speak to a healthcare provider if you see or feel changes in your breasts.

What Causes Triple-Negative Breast Cancer? 

A study published in 2015 found that TNBC is one of the least understood types of breast cancer.

Generally, breast cancer occurs because of changes in your DNA, or genetic material. You may inherit those changes. For example, BRCA1 and BRCA2 genetic mutations increase breast cancer risk. People with a BRCA1 mutation are more likely to have TNBC than others.

Changes in your DNA can also occur because of environmental or lifestyle factors. Still, in most cases, the cause of breast cancer is unknown.

Risk Factors

Compared to other breast cancers, TNBC is more likely to occur in premenopausal people under 40 years old.

Other factors that increase your risk for TNBC include:

  • Alcohol consumption
  • Dense breast tissue
  • Genetics
  • Getting your period earlier than 12 years old
  • Giving birth to your first child when you're older than 30 years old
  • Obesity
  • Prior radiation therapy to the breast or chest

There are many common misconceptions about factors that increase breast cancer risk. Not enough evidence exists to show the following factors influence breast cancer risk:

  • Abortion
  • Aluminum-based antiperspirants
  • Bras
  • Fertility drugs

How Is Triple-Negative Breast Cancer Diagnosed?  

As with all types of cancer, early detection and treatment are crucial. 

Healthcare providers can use the following tools to evaluate whether you have breast cancer:

  • Blood tests: A healthcare provider may measure multiple substances, such as blood sugar, electrolytes, fats, and proteins.
  • Breast biopsy: This procedure removes your cells or tissues so a healthcare provider can examine them.
  • Family and personal health history: About 5% to 10% of all cancers develop due to inherited gene mutations. Sometimes, a shared environment or similar lifestyles of family members can also heighten cancer risk.
  • Imaging tests: These can include a breast ultrasound, breast MRI, or mammogram.
  • Physical exam: A healthcare provider will check your breasts for any signs of cancer, such as dimpling or lumps.

Those tests can diagnose breast cancer but cannot show the type of breast cancer like TNBC. After diagnosis, a healthcare provider will likely order more tests to determine the stage and type of breast cancer.

To determine if the cancer is triple-negative, you will need tests to check the cancer cells for HER2 and estrogen and progesterone receptors. A healthcare provider may also order genetic tests.

Breast Cancer Screening Guidelines

The U.S. Preventive Services Task Force (USPSTF) advises that women get mammograms every other year, beginning at age 50. More research is needed on whether people with dense breasts need additional screenings and the potential benefits and risks of screening people older than 74.

Stages of Triple-Negative Breast Cancer

After identifying TNBC, a healthcare provider may stage the illness. Generally, breast cancer stages vary depending on whether and how much cancer cells have spread. Staging TNBC helps healthcare providers know how to treat the disease.

Healthcare providers use the following criteria to stage TNBC:

  • Stage 0: This is a pre-invasive breast cancer called ductal carcinoma in situ (DCIS). In stage 0 TNBC, abnormal cells line the breast milk ducts but have not spread to nearby breast tissue.
  • Stage 1: Cancer cells have spread to nearby breast tissue and formed a tumor less than or equal to 20 millimeters. A small number of cancer cells may have spread to nearby lymph nodes. Cancer cells have not spread to distant body parts.
  • Stage 2: Tumors measure between 20–50 millimeters. As with stage 1 TNBC, some cancer cells may have spread to nearby lymph nodes but not distant body parts.
  • Stage 3: Tumors may be larger than 50 millimeters. Cancer cells may have spread to nearby lymph nodes but not distant body parts. 
  • Stage 4: TNBC advances to stage 4, called metastatic breast cancer if it spreads to distant organs.

Treatments for Triple-Negative Breast Cancer

There are fewer treatments for TNBC than for other types of breast cancers. Hormone therapy and targeted HER2 drugs do not work on a hormone receptor-negative disease like TNBC. Those treatments also do not work since the cancer cells have little or no HER2.

TNBC treatments may depend on the stage and whether the cancer is recurrent.

Stage 1–3

For stage 1–3 TNBC, some of the most common treatments include:

  • Chemotherapy: This is one of the most common treatments for all stages of TNBC. Chemo is a systemic treatment, meaning it targets the whole body. The medicines that chemo uses stop the growth of cancer cells. Side effects may include hair loss, nausea, and tiredness.
  • Surgery: People may get surgery before or after chemo. Surgery may include a lumpectomy or mastectomy. A lumpectomy removes the lump from the breast. A mastectomy removes the whole breast and nearby lymph nodes. A surgeon may be able to rebuild the breast during the surgery.
  • Radiation therapy: This uses high-energy rays or particles to destroy cancer cells at specific sites. A healthcare provider may advise radiation therapy after surgery if the tumor is large or cancer cells have spread. 

Stage 4

At stage 4, TNBC is not curable. Still, healthcare providers can treat TNBC to prolong lives and reduce symptoms. 

Treatment for stage 4 TNBC includes:

  • Chemotherapy
  • Drug therapies (e.g., immunotherapy or targeted therapy)
  • Radiation therapy
  • Surgery

Recurrent Triple-Negative Breast Cancer

Healthcare providers can treat recurrent TNBC that has not spread with chemotherapy and immunotherapy. 

In 2020, the Food and Drug Administration approved Trodelvy (sacituzumab govitecan-hziy), a medication to treat recurrent TNBC that has spread. Trodelvy is a targeted drug therapy that attacks cancer cells in the body.

You can only take Trodelvy after you have tried at least two treatments. The medication has side effects such as low white blood cell counts and severe diarrhea. Low white blood cell counts weaken the immune system and raise the risk of infectious illnesses.

As of June 2023, clinical trials for TNBC treatments are ongoing. Participating in them can give you access to new drugs or therapies.

How To Prevent Triple-Negative Breast Cancer

There's no sure way to prevent breast cancer, including TNBC.

Some lifestyle changes may reduce your risk of TNBC, such as:

Regular breast cancer screenings are essential to improve your treatment outlook. No matter the risk, pay attention to any changes in your breasts. Contact a healthcare provider right away if you notice any changes.

Complications

Complications from TNBC may come from treatments, including chemotherapy, radiation therapy, and surgery.

Chemo may harm your healthy cells since it cannot only target cancer cells. As a result, you may have complications, such as:

  • Diarrhea
  • Hair loss
  • Memory loss, or "chemo brain"
  • Menopause symptoms (i.e., hot flashes, irregular periods, and vaginal dryness)
  • Nausea
  • Nerve problems
  • Vomiting

Like chemo, radiation therapy may target and attack your healthy cells, causing complications. Radiation therapy may cause side effects like:

  • Changes to the skin
  • Chronic heart and lung complications
  • Fatigue
  • Hair loss
  • Nerve problems
  • Pain

Generally, surgery comes with complications, such as:

  • Bleeding
  • Cosmetic issues
  • Infection
  • Loss of sensation in the chest area or reconstructed breasts
  • Pain
  • Scarring

Living With Triple-Negative Breast Cancer 

TNBC is a fast-growing breast cancer that is more likely to return after treatment than other types. As a result, TNBC has a lower five-year survival rate than other breast cancers. 

At all stages, TNBC has a five-year survival rate of 77%. Your survival rate may vary depending on whether and how much the cancer cells have spread. 

Having TNBC or any type of breast cancer can be hard on your body and mind. Eating a balanced diet, prioritizing your sleep, and staying active if you can are essential.

Of note: You do not have to rebuild the shape of your breast if you have a mastectomy. You do not have to do anything if you do not want to. Other options include padding the inside of your bra or wearing a breast form. 

A Quick Review

TNBC is an aggressive cancer more likely to return than other breast cancers. Early diagnosis and treatment are essential to increasing the five-year survival rate of TNBC. 

Experts advise preventative mammograms every other year, starting at age 50. Consult a healthcare provider immediately if you notice any changes to your breasts.

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