Triple-Negative Breast Cancer (TNBC) Explained

This page explains triple-negative breast cancer: what the name means, who it affects, and how early-stage and metastatic disease are treated.

When breast cancer is diagnosed, the tissue is tested for three things. These are the estrogen receptor (ER), the progesterone receptor (PR), and a protein called HER2. When all three come back negative, the cancer is called triple negative.

The name says what the cancer lacks. It does not say how serious it is. But it matters. Hormone-blocking pills such as tamoxifen and aromatase inhibitors latch onto the hormone receptors. HER2 drugs such as trastuzumab latch onto HER2. If none of those targets is there, those pills cannot help. Other tools do the work instead. Those are chemotherapy, immunotherapy, surgery and radiation. Chemotherapy is often the first treatment.

Triple-negative disease makes up roughly 10 to 15 percent of breast cancers. It is found more often in Black women. It is also more common in women who have not been through menopause, and in people who carry an inherited BRCA1 mutation. It tends to grow and spread faster than other invasive breast cancers. The risk of it coming back is highest in the first few years after treatment.

Ask whether genetic counseling and testing are right for you. NCI notes that breast cancers in people with a BRCA1 change are more likely to be triple negative. A BRCA1 or BRCA2 mutation can change which surgery you pick. It also opens up PARP inhibitors, a type of targeted drug, such as olaparib or talazoparib. And it gives your relatives facts they can act on. Ask for the referral early.

For some tumors, chemotherapy is given before surgery. This is called neoadjuvant treatment. It can shrink the tumor enough to allow a smaller operation. It also shows your team whether the cancer is responding while you are still being treated.

For high-risk early-stage disease, pembrolizumab may be added to that chemotherapy. Pembrolizumab is an immunotherapy drug. It is then kept going on its own after surgery.

At surgery, the removed tissue is examined. If no invasive cancer is left, that is called a pathologic complete response. It is linked to better long-term outcomes. If some cancer is left, that is not a failure. Your team may suggest more treatment after surgery. One option is the PARP inhibitor olaparib, if you carry a BRCA mutation.

Radiation is often advised after lumpectomy. It is sometimes advised after mastectomy too. That depends on tumor size and lymph nodes.

Once triple-negative breast cancer has spread, the aim shifts. Now the goal is to hold it in check for as long as possible. Quality of life is protected at the same time. Options include:

• Chemotherapy. This is usually the first treatment.
• Pembrolizumab with chemotherapy. This is used when the tumor makes enough of a protein called PD-L1.
• Sacituzumab govitecan. This is an antibody-drug conjugate. It carries chemotherapy to cells that show the Trop-2 protein. It is used after at least two earlier treatments, including at least one for metastatic cancer.
• PARP inhibitors such as olaparib or talazoparib. These are for people with an inherited BRCA1 or BRCA2 mutation.
• Clinical trials. In this subtype they are often worth weighing at every decision point, not just at the end.

Treatment usually goes on until it stops working, or until side effects get too heavy. Then it is changed. Palliative care alongside treatment helps with pain, fatigue and sleep.

Ask for your full pathology report and keep a copy. Write down which chemotherapy drugs you have had. That determines what comes next. Report side effects early, such as fatigue, neuropathy (nerve damage that causes numbness or tingling) and signs of low blood counts.

• Call 911 or go to an emergency department if you cannot catch your breath, your chest hurts, or your heartbeat turns irregular while on pembrolizumab. Also go now for bleeding that will not stop, or for widespread blistering or peeling of the skin. Do not drive yourself.
• Call 911 or go to an emergency department if you pass black, tarry or sticky stool, or there is a lot of blood in your stool (MedlinePlus). Do not drive yourself.
• Call your care team this minute, day or night, if your temperature hits 100.4°F (38°C) or higher, or you get chills and feel unwell during chemotherapy. CDC says a fever during chemotherapy is a medical emergency, because with low blood counts an infection can move within hours. If they cannot be reached fast, go to an emergency department and lead with the fact that you are on chemotherapy.
• Call your care team right away if you have new diarrhea, any blood or mucus in your stool, or bad belly pain while on immunotherapy (MedlinePlus). Do not wait for a certain number of stools. Use the 24-hour number on your treatment card. MedlinePlus says to call your doctor immediately or get emergency treatment for these. Immune-related inflammation of the bowel is treatable, and treated sooner it is milder.
• Call your care team right away if your skin or the whites of your eyes look yellow, or you bruise or bleed easily.
• Call your care team within a day or two if numbness or tingling in your hands or feet is new or spreading. Reporting neuropathy early is what lets your team adjust the dose instead of stopping the drug.

• NCI: Breast Cancer Treatment (PDQ®) Patient Version
• American Cancer Society: Triple-Negative Breast Cancer
• NCI drug information: sacituzumab govitecan-hziy
• NCI drug information: olaparib
• NCI: BRCA Gene Mutations Fact Sheet
• NCI: Triple-Negative Breast Cancer Treatment
• DailyMed: KEYTRUDA (pembrolizumab) prescribing information
• MedlinePlus: Pembrolizumab Injection
• CDC — Fever and Cancer Treatment
• NCI: Infection and Neutropenia during Cancer Treatment