Triple-negative breast cancer

While some breast cancers express hormone receptors or have too many copies of the HER2 gene, other breast cancers may not have these characteristics. Triple-negative breast cancers (TNBC) do not express estrogen receptors, progesterone receptors, or HER2 receptors. About 10% to 15% of breast cancers are triple-negative.

TNBC tends to be more aggressive than other breast cancers. This can happen for a few reasons:

• The grade of triple-negative breast cancer is usually higher than that of other breast cancers. High-grade cancer cells divide and multiply faster than low-grade cancer cells.
• TNBC has a higher risk of recurrence (likelihood to come back) than hormone receptor-positive or HER2-positive breast cancers, but this is dependent on stage.
• In general, there are fewer treatment options available for triple-negative breast cancer than there are for hormone receptor-positive and HER2-positive breast cancer. This is because:
  • Hormone receptor-positive and HER2-positive breast cancers have cell receptors — proteins in or on the cell that receive signals to grow and multiply. Treatments for these cancers can target the receptors and block growth signals or work in other ways to directly impact the cancer cells.
  • TNBC doesn’t have hormone or HER2 receptors, so people with this diagnosis are not eligible for medicines that target hormone receptor-positive or HER2-positive breast cancer. However, recently there have been improvements in treatment options for patients with TNBC.

It’s important to know that even though hormone receptor and HER2 receptor-targeting medicines can’t be used to treat TNBC, other treatments can be given to certain people diagnosed with TNBC. Recent advances in TNBC treatment include the approval of immunotherapy for early-stage and metastatic TNBC. Treatment can also include chemotherapy (for all stages) and targeted therapies for metastatic TNBC.

TNBC is more common in younger women, Black women, and women with inherited BRCA1 mutations. In men, TNBC is rare, although it can occur.

We know it can be scary to hear that you have TNBC. We invite you to contact our Breast Cancer Helpline to be matched with a trained volunteer who also has TNBC. Our volunteers can talk with you about their experience and provide emotional support. You can also visit our pages on finding support and coping with breast cancer for more ways to connect and navigate the emotions that can come up with a breast cancer diagnosis.

Here, you can find information about symptoms, diagnosis, and treatment options for TNBC. We’ll also talk about how TNBC impacts different racial and ethnic groups, and we’ll clarify some myths about this diagnosis.

Signs & symptoms

The symptoms of triple-negative breast cancer are the same symptoms common to most breast cancers. Symptoms can include:

• A new lump in the breast
• Changes in the skin, such as redness, dryness, flaking, or thickening of the nipple or breast skin that can sometimes be mistaken as an infection
• Nipple discharge that is not breast milk, with or without bleeding
• A nipple that turns inward
• Swollen lymph nodes under the arm or near the collarbone

A certain type of breast cancer called inflammatory breast cancer (IBC) is often triple-negative. IBC has unique symptoms, including breast swelling, a feeling of heat in the breast, and skin dimpling or puckering, including an orange-peel appearance.

Breast cancer signs are different than symptoms. Often, a person will experience symptoms on their own and then report them to their doctor, who may recommend tests to learn more. Signs are identified by a doctor or radiologist during a breast exam or test, such as a mammogram or biopsy, that can help confirm a diagnosis.

Diagnosis

All breast cancers are diagnosed in similar ways. If you notice a lump or other symptom and report it to your doctor, or if a routine mammogram shows a suspicious area, imaging tests may be recommended to take a closer look.

Imaging tests to diagnose breast cancer can include:

• Mammogram. A mammogram is a type of x-ray used to look for changes in the breast.
• Ultrasound. Ultrasound uses high frequency sound waves to take pictures of areas inside the body.
• MRI (magnetic resonance imaging). MRI uses magnets and radio waves to create 3D images of the breast.

If an imaging test shows potential signs of breast cancer, your doctor may recommend a breast biopsy. A biopsy is a procedure that removes a small piece of tissue. The tissue sample taken from the breast is then tested by a pathologist to confirm the presence or absence of cancer.

There are three types of breast biopsy:

• Fine-needle aspiration: In this procedure, a very thin needle is used to remove a sample.
• Core needle biopsy: This procedure is similar to fine-needle aspiration, but uses a thicker needle to take a larger sample.
• Surgical/excisional biopsy: In this type of biopsy, part or all of the tumor is removed from the breast. Surgical biopsy typically requires that you be under anesthesia during the procedure.

After a breast biopsy, the removed tissue sample is analyzed under a microscope. If cancer cells are found, tests are performed to learn more about the cells. One of those tests, called an immunohistochemical staining assay or IHC test, will show whether the cancer cells have estrogen receptors, progesterone receptors, HER2 receptors, or all three. In some cases, if IHC testing does not clearly confirm HER2 positivity or negativity, another test called FISH (fluorescence in situ hybridization) may be needed.

• If the breast cancer cells test negative for all three receptors, the cancer is called triple-negative.
• If the cancer tests positive for hormone receptors, it is called hormone receptor-positive breast cancer.
• If it tests positive for HER2 receptors, it’s called HER2-positive breast cancer.

Your doctor will share your results with you in a document called your pathology report.

Video: Ask the expert: Triple-negative breast cancer

Dr. Foluso Ademuyiwa answers questions about symptoms, diagnosis, side-effects, and treatment options for early-stage and metastatic TNBC.

Treatment

For early-stage triple-negative breast cancer, chemotherapy and sometimes immunotherapy are recommended as main treatments. If you have metastatic breast cancer, you may be offered immunotherapies or targeted therapies in addition to chemotherapy.

Treatment options are based on the confirmation of triple-negative status of the cancer, the stage, and a few other factors, including:

• Whether the cancer has traveled to the lymph nodes near the breast
• The size of the main tumor
• Details of tests in your pathology report, such as the tumor grade, which shows how quickly the cancer cells are dividing
• Whether the tumor cell and immune cells express a protein called PDL1

For early-stage TNBC, surgery and chemotherapy are often recommended. Sometimes chemotherapy is given prior to surgery (neoadjuvant therapy) and immunotherapy may also be added to treatment.

Early-stage TNBC can also be treated with an immunotherapy called pembrolizumab (Keytruda), which is approved in combination with chemotherapy for early-stage TNBC that has a high risk of coming back. Immunotherapy such as pembrolizumab uses the body’s own immune system to slow or stop cancer growth. For early-stage breast cancer with a high risk of recurrence, pembrolizumab is approved to be given with chemotherapy before surgery, followed with pembrolizumab by itself after surgery.

Your physician may decide to add other medications, such as capecitabine or a PARP inhibitor after surgery, depending on other factors. Olaparib is a PARP inhibitor approved to treat people with an inherited BRCA1 or BRCA2 mutation diagnosed with high-risk, triple-negative, early-stage breast cancer that has already been treated with surgery and chemotherapy.

For metastatic triple-negative breast cancer, the following treatments are available:

• Immunotherapy:
  • Pembrolizumab (Keytruda) is the only immunotherapy currently approved to treat metastatic TNBC.
• PARP inhibitors are medicines that stop an enzyme called PARP from repairing cancer cell DNA. There are two PARP inhibitors available for people with metastatic TNBC. In order to receive these medicines, you must also carry an inherited BRCA mutation.
  • Olaparib (Lynparza)
  • Talazoparib (Talzenna)
• Targeted therapy is medicine that targets specific features of cancer cells that help them grow and spread. There is one targeted therapy approved to treat metastatic TNBC:
  • Sacituzumab govitecan (Trodelvy)
• Platinum-based chemotherapy is chemotherapy that damages DNA in cancer cells and destroys them. This kind of chemotherapy can treat metastatic TNBC in people who carry a BRCA mutation. The chemotherapies include:
  • Carboplatin (Paraplatin)
  • Cisplatin (Platinol)

Effects on different races & ethnicities

In general, young women and Black women have a higher chance of being diagnosed with triple-negative breast cancer than older women and women of other races or ethnicities. The American Cancer Society’s Breast Cancer Facts & Figures 2019-2020 reports that of all breast cancers diagnosed in Black women, about 21% are triple-negative. In comparison, only 10% of breast cancer diagnosed in non-Hispanic white women and Asian/Pacific Islanders is triple-negative, and only 12% of breast cancer diagnosed in American Indian/Alaska Native women and Hispanic women is triple-negative.

Though Black women have the highest chance of being diagnosed with triple-negative disease compared to women of other races, the rate of triple-negative diagnosis in Black women is still lower than diagnosis of other breast cancers. Like women from all racial and ethnic groups, Black women are most often diagnosed with hormone receptor-positive breast cancer. Of breast cancers diagnosed in Black women, 61% are hormone receptor-positive.

3 myths about triple-negative breast cancer

MYTH: People with triple-negative breast cancer can have the same treatments as all other people with breast cancer.

FACT: It’s possible you’ll get some of the same types of chemotherapy that are given for hormone receptor-positive or HER2-positive breast cancers. But triple-negative breast cancer can’t be treated with some of the treatments used in other breast cancers, such as hormonal therapies or HER2-targeting therapies. Early-stage TNBC is usually treated with chemotherapy, and immunotherapy is sometimes combined with chemotherapy. Metastatic TNBC can be managed with chemotherapy as well as some immunotherapies (if tumor and immune cells express a protein called PD-L1), targeted therapies, and PARP inhibitors (if you have an inherited BRCA mutation). We know that some people in your life may not understand the ways that TNBC is different than other breast cancers, and that they might not understand why treatments given to other people may not be the right kind of treatment for you. Having to explain this can be frustrating, especially if you are just learning about this diagnosis yourself. Connecting with others who share your experience can help.

MYTH: Triple-negative breast cancer is always hard to treat.

FACT: TNBC is often more aggressive than some other types of breast cancer. But there are some very effective treatments for triple-negative disease. If you see statistics about life expectancy that worry you, or you hear your doctor or others say TNBC is hard to treat, remember that statistics generalize the experiences of large numbers of people. They don't reflect the experience of one person, and may not describe the experience you have. Your doctor’s prediction of how well your treatment will work depends not only on its triple-negative status, but also on the tumor size and whether the cancer has traveled to the lymph nodes, the small glands in the armpit and other areas near the breast.

MYTH: Only Black women get triple-negative breast cancer.

FACT: Triple-negative breast cancers affect people of all races. Breast cancers in Black women are more likely to be triple-negative than those in white women.