Treatment of Triple-negative Breast Cancer

Triple-negative breast cancer (TNBC) doesn’t have estrogen or progesterone receptors and also makes too little or none of the HER2 protein. Because the cancer cells don't have these proteins, hormone therapy and drugs that target HER2 are not helpful, so chemotherapy (chemo) is the main systemic treatment option. And even though TNBC tends to respond well to chemo initially, it also tends to come back (recur) more frequently than other breast cancers.

Stages I-III triple-negative breast cancer

Surgery first: If the early-stage TNBC tumor is small enough to be removed by surgery, then breast-conserving surgery or a mastectomy with a check of the lymph nodes may be done In certain cases, such as with a large tumor or if the lymph nodes are found to have cancer, radiation may follow surgery. You might also be given chemo after surgery (adjuvant chemotherapy) to reduce the chances of the cancer coming back. For women who have a BRCA mutation and at surgery are found to have:

• A tumor larger than 2cm but no bigger than 5cm OR
• 1 to 3 axillary (underarm) lymph nodes with cancer

the targeted drug olaparib (Lynparza) might be given for a year after adjuvant chemo.  When given this way, it can help some women live longer.

Surgery second: Chemo is often given before surgery (neoadjuvant chemotherapy) by itself or with pembrolizumab (Keytruda) to shrink a large tumor and/or lymph nodes with cancer. If cancer is still found in the tissue removed by surgery after neoadjuvant chemo has been given, your doctor may recommend:

• an oral chemo drug called capecitabine (Xeloda) for 18 to 24 weeks. This might help some women live longer.  
• more pembrolizumab after surgery (adjuvant treatment) to reduce the chances of the cancer coming back.
• the targeted drug olaparib for one year for women who have a BRCA mutation to help lower the chance of the cancer recurring. When given this way, it can help some women live longer.  

Stage IV triple-negative breast cancer

Chemo is often used first when the cancer has spread to other parts of the body (stage IV). Common chemo drugs used include anthracyclines, taxanes, capecitabine, gemcitabine, eribulin, and others. Chemo drugs might be used alone or in combination.  

For women with TNBC who have a BRCA mutation and whose cancer no longer responds to common breast cancer chemo drugs, other platinum chemo drugs (like cisplatin or carboplatin) or targeted drugs called PARP inhibitors (such as olaparib [Lynparza] or talazoparib [Talzenna]), may be considered.

For advanced TNBC in which the cancer cells have the PD-L1 protein, the first treatment may be immunotherapy (pembrolizumab) plus chemo . The PD-L1 protein is found in about 1 out of 5 TNBCs.

For advanced TNBC in which at least 2 other drug treatments have already been tried, the antibody-drug conjugate sacituzumab govitecan (Trodelvy) might be an option.

For advanced TNBC in which the cancer cells show high levels of gene changes called microsatellite instability (MSI) or changes in any of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2), immunotherapy with the drug pembrolizumab might be used. Pembrolizumab might also be an option for TNBC that has a high tumor mutational burden (TMB-H) which is a measure of the number of gene mutations (changes) inside the cancer cells. Cells that have many gene mutations (a high TMB) might be more likely to be recognized as abnormal and attacked by the body’s immune system.

Surgery and radiation may also be options in certain situations. 

See Treatment of Stage IV (Metastatic) Breast Cancer for more information.

Recurrent triple-negative breast cancer

If TNBC comes back (recurs) locally, cannot be removed with surgery, and makes the PD-L1 protein, immunotherapy with the drug pembrolizumab along with chemotherapy is an option. Other treatments might be options as well, depending on the situation.

If the cancer recurs in other parts of the body, options might include chemotherapy or the antibody-drug conjugate sacituzumab govitecan (Trodelvy).

Regardless of the stage of the cancer, participation in a clinical trial of new treatments for TNBC is also a good option because TNBC is uncommon and tends to have a poor prognosis (outcome) compared to other types of breast cancer, and because these studies often allow patients to have access to drugs not available for standard treatment.