Triple Negative Breast Cancer

Triple negative breast cancer is an aggressive form of breast cancer that doesn’t respond to the same treatments as other types. Understanding what makes this cancer different can help you make informed decisions about your care and feel more in control during your journey.

Table of contents

• What is triple negative breast cancer?
• Who is most affected?
• Signs and symptoms
• How doctors diagnose this cancer
• Treatment approaches
• What to expect

TNBC, basal-like breast cancer

What is triple negative breast cancer?

Triple negative breast cancer, often called TNBC, is a type of breast cancer that behaves differently from other breast cancers. To understand why it’s called “triple negative,” you need to know that doctors test every breast cancer for three important markers: the estrogen receptor (a protein that can attach to the female hormone estrogen), the progesterone receptor (a protein that can attach to the hormone progesterone), and HER2 (a protein that tells breast cells to grow).^[2]

When all three of these tests come back negative, the cancer is considered triple negative breast cancer.^[2] This means the cancer cells don’t have these receptors or proteins that help other breast cancers grow.^[6] Think of receptors like locks that only certain keys can open. Because TNBC cells don’t have these locks, treatments that work for other breast cancers by targeting these receptors won’t work as well for TNBC.^[6]

Triple negative breast cancer represents about 10 to 15 percent of all breast cancer cases.^[3] It tends to grow rapidly and is more likely to spread beyond the breast before diagnosis than other types of breast cancer.^[2] It also has a higher likelihood of coming back, especially in the first three to five years after treatment, though if it doesn’t return by then, the risk drops substantially.^[20]

Most triple negative breast cancers have what doctors call a basal-like genetic pattern. This term means the cancer cells look somewhat like the cells that line the breast ducts, the tubes where milk travels in the breast.^[4] About 70 to 90 percent of triple negative breast cancers are basal-like.^[4]

Who is most affected?

While triple negative breast cancer can affect anyone, certain groups of people face higher risk. Women younger than 40 are more commonly diagnosed with this type of breast cancer.^[2] In fact, TNBC is disproportionately diagnosed in young women, who often face tumors that grow quickly and are frequently discovered at more advanced stages.^[20]

Race and ethnicity also play a significant role. Black women are particularly affected by this disease. The incidence of TNBC is about two times higher in Black women compared to White women.^[3] Nearly 20 percent of breast cancers diagnosed in Black women are triple negative.^[3] Hispanic women and women of Indian descent also see this type of breast cancer more commonly.^[2]

Genetic factors matter as well. Women who have a mutation in the BRCA1 gene (a gene that normally helps prevent cancer from growing) are at higher risk for developing triple negative breast cancer.^[2] Most breast cancers that develop in people with a BRCA1 mutation are triple negative.^[20] There is also a connection between TNBC and mutations in the BRCA2 gene.^[6]

It’s important to understand that most people diagnosed with breast cancer, including triple negative breast cancer, do not have a strong family history of the disease. They also often do not carry genetic mutations like BRCA1 or BRCA2.^[21]

Signs and symptoms

Triple negative breast cancer may show the same signs and symptoms as other common types of breast cancer. However, most breast cancers are actually detected before any symptoms appear through regular screening tests like mammograms.^[3]

Possible signs and symptoms you should watch for include:^[3][6]

• A new lump or mass in your breast
• Swelling of all or part of a breast
• Skin dimpling on the breast
• Breast or nipple pain
• A nipple turning inward (nipple retraction)
• Nipple or breast skin that’s red, dry, flaking, or thickened
• Nipple discharge
• Swollen lymph nodes under the arm or near the collarbone

Having certain symptoms doesn’t mean you have breast cancer. But don’t hesitate to talk to a healthcare provider if you notice changes in your breasts.^[6] It’s also important to have regular mammograms that may detect cancer before it causes symptoms.^[6]

One important thing to know about triple negative breast cancer is that it can grow fast, sometimes even in the time between annual mammograms.^[21] This is why you shouldn’t watch or wait on lumps for months at a time. If you find something unusual, insist on screenings. Time is more important than we realize.^[21]

Dense breast tissue, which is very common, can make it harder to detect breast cancer on a mammogram. If you’ve been told your breast tissue is dense, you should do more regular breast self-exams to know your body and strongly consider following up regular mammograms with ultrasound if you have the means.^[21]

How doctors diagnose this cancer

Confirming a diagnosis of triple negative breast cancer starts with a biopsy (a procedure to remove a sample of breast tissue for testing).^[2] Before the biopsy, a healthcare provider will examine your breast and ask if you’ve noticed changes. They’ll do imaging tests including mammogram, breast MRI, and breast ultrasound.^[6]

If imaging tests detect cancer, a surgical specialist or a radiologist will do a breast biopsy to get tissue samples. A medical specialist will examine the tissue under a microscope.^[6] Your care team will send your tissue to the laboratory for analysis to determine cell type, how aggressive the cancer is (called the grade), and whether the cancer cells have hormone receptors.^[2]

The lab will check the status of estrogen receptor, progesterone receptor, and HER2. If those three tests are negative, the cancer is considered triple negative breast cancer.^[2] The lab will also analyze your cancer cells’ genetic makeup to determine if they have other markers.^[2]

Your doctor may do another test to identify any germline mutations (mutations that occur in a parent’s reproductive cells and can be passed from parent to child). You can inherit these mutations from either parent.^[6]

Your cancer care team will use test results to set a cancer stage. Cancer staging information helps them plan treatment.^[6] The stages range from Stage 0, where cancer cells are in your breast ducts but haven’t spread, to Stage III, which doctors may call locally advanced breast cancer.^[6]

Treatment approaches

Because triple negative breast cancer cells don’t have the receptors that other breast cancers have, medicines like tamoxifen (which targets the estrogen receptor) and trastuzumab or Herceptin (which targets HER2) are not helpful in treating this disease.^[4] The vast majority of women with this diagnosis will need chemotherapy (medicine that kills cancer cells everywhere in your body).^[2]

Chemotherapy

Chemotherapy has been shown to be the most effective treatment for triple negative breast cancer.^[4] The reason is that chemotherapy works better than other treatments at killing cancer cells that divide quickly, which is very common in triple negative disease. When triple negative breast cancers are found early, response rates to chemotherapy are high.^[11]

Chemotherapy may be given before or after surgery.^[11] If you have a tumor that is very large or you have a sizable tumor and want a less extensive surgery, your doctor may recommend chemotherapy before surgery, also called neoadjuvant therapy. This therapy shrinks the tumor and helps your doctor learn how sensitive the tumor is to chemotherapy.^[11]

Doctors try to lessen the chance of the cancer coming back and spreading to other parts of the body (called metastatic recurrence) by treating the whole body, including any areas where very tiny cancer cells may have traveled.^[11]

Surgery

Your doctor will likely recommend some type of surgery, with the goal of removing the cancer from your breast.^[11] In a lumpectomy, also called breast-conserving surgery, the surgeon removes the tumor plus a small rim of normal tissue around the tumor. Your doctor may also recommend a mastectomy, which involves removing more breast tissue.^[11]

Radiation therapy

Radiation is a local therapy that kills cancer cells left after surgery in the area where the breast cancer was found.^[11] It helps protect you from the cancer coming back in the same place. Radiation usually is given from outside your body. If you have a lumpectomy, you will need radiation to kill any cancer cells left in the breast and sometimes in the underarm area.^[11]

Immunotherapy

Using medicines, immunotherapy boosts your immune system so that it can do a better job of recognizing and fighting cancer cells.^[15] Pembrolizumab (brand name Keytruda) is an immunotherapy drug that was approved for advanced TNBC in 2020. Adding pembrolizumab to chemotherapy for advanced TNBC improves survival. Recently, pembrolizumab was found to improve outcomes for women with early stage TNBC and was approved for use in those with high-risk, early-stage disease.^[15]

Targeted drug therapies

Antibody-drug conjugates (also known as ADCs) help target and deliver chemotherapy directly into cancer cells and surrounding tissue, leading to higher effectiveness and reduced damage to surrounding normal, healthy cells.^[15] The ADC sacituzumab (brand name Trodelvy) is approved for locally advanced and/or metastatic TNBC for those who have already received two or more treatments (at least one of them for metastatic disease). Sacituzumab significantly improves survival compared to standard chemotherapy.^[15]

Treatment for metastatic TNBC

Once TNBC has spread to distant organs, it is not usually considered curable. The goal of treatment becomes to control the cancer and its symptoms.^[15] The primary treatment remains chemotherapy. Many patients receive a single drug for as long as they respond and then move onto second and third lines of therapy. In other cases, drugs are combined with each other.^[15]

About one-third of patients with metastatic TNBC will have an initial response to chemotherapy. Their tumors will either shrink or stop growing. The problem is that the cancer often becomes resistant, meaning that the cancer cells stop responding to the therapy. With each new drug, the chances of responding go down and the response time becomes shorter as the ability of the cancer cells to resist the treatment goes up.^[15]

What to expect

Your doctor’s prediction of how well your treatment will work depends on the tumor size and whether the cancer has traveled to the lymph nodes or tissues near the breast, just as much as it does on its triple negative status.^[4] There are some very effective treatments for triple negative breast cancer, and your doctor will work with you to determine the best approach.^[4]

Triple negative breast cancer has a higher risk of recurrence in the first three to five years. However, if it does not return by then, the risk drops substantially.^[20] Recent advances are improving treatment outcomes for people with this disease.^[2] Recent research shows combining certain cancer drugs may help people live longer with triple negative breast cancer.^[6]

The diagnosis of metastatic TNBC is frightening for women and the people who love them. These cancers can be treated, and there are increasing numbers of therapies that are helping women with metastatic TNBC, along with hundreds of clinical trials testing new approaches.^[15]

Medical researchers continue to study new treatments. Researchers are working to understand how triple negative breast cancer grows and spreads, how the immune system may recognize and fight it, and to develop new treatments for the disease.^[2]