Treatment Options When Metastatic Triple-Negative Breast Cancer Becomes Unresponsive to Chemotherapy

Even though chemotherapy is the standard treatment for metastatic triple-negative breast cancer (mTNBC), it’s not uncommon for these drugs to stop working eventually.

To understand why, it helps to keep in mind that breast cancer is made up of different types of cancerous cells. And while chemotherapy can be effective at destroying some kinds of cells, it may not be able to destroy other kinds, says Marisa Weiss, MD, chief medical officer and founder of Breastcancer.org, a patient-focused resource for people with breast cancer.

What’s more, breast cancer cells can also become resistant to chemotherapy over time, which makes the treatment less effective, says Mahmoud Charif, MD, a professor of clinical internal medicine at the University of Cincinnati School of Medicine. This is especially the case for metastatic triple-negative breast cancer, which tends to be a more aggressive form of cancer.

Chemotherapy isn’t your only option. If these drugs have stopped working, your doctor may recommend switching to a different type of breast cancer medication or adding other resources to your treatment plan. “There can be a whole list of other options besides chemotherapy,” says Dr. Weiss.

Some of these treatment options include:

• Immunotherapy “Immunotherapy works by stimulating the body’s immune system to recognize and destroy cancer cells,” says Amy Tiersten, MD, a professor of hematology and medical oncology and clinical director of breast medical oncology at Mount Sinai in New York City. When used to treat metastatic triple-negative breast cancer, immunotherapy medication targets a protein called programmed cell death protein 1 (PD-1), which is found on immune cells in the body called T cells. PD-1 tells T cells not to attack other cells. So by “turning off” PD-1, the immune system is better able to fight off cancer cells. Immunotherapy is most effective when combined with chemotherapy, says Dr. Tiersten.

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  A review found immunotherapy can be effective for both early and advanced triple-negative breast cancer. Identifying predictive biomarkers to help select the right treatment, plus novel treatment combinations and more specific therapeutic targets, will continue to improve outcomes with immunotherapy.

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• PARP Inhibitors These medications can help prevent cancer cells from surviving in the body. They do so by blocking an enzyme called poly (ADP-ribose) polymerase (PARP), which helps repair DNA damage in both healthy cells and cancer cells. By inhibiting the PARP enzyme, the cancer cells can become less likely to repair themselves and survive. PARP inhibitors are only given to people who have the BRCA1 or BRCA2 gene mutation, though, partly because breast cancers related to BRCA 1 and BRCA 2 seem to be particularly sensitive to PARP inhibitors, which are pills taken by mouth.

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• Antibody-Drug Conjugates These drugs combine an antibody therapy and a chemotherapy drug, which work together to kill cancer cells. Here’s how it works: The antibody carries the chemotherapy molecules to the cancer cells. Then the antibody binds to a certain receptor on the cancer cell and releases the chemotherapy drug, which enters the cell and kills the tumor, says Dr. Charif. When used to treat metastatic triple-negative breast cancer, antibody-drug conjugates are given by IV.

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• Clinical Trials Ongoing clinical trials give people with metastatic breast cancer a chance to try new breast cancer treatments that may eventually become part of standard practice. If you are interested in joining a clinical trial, talk to your oncologist to see if there’s one that might be right for you. You can check the availability of trials at ClinicalTrials.gov.

If chemotherapy has stopped working, you may experience changes in your mood. “The realization that chemo is no longer effective can be devastating,” says Francisco J. Esteva, MD, PhD, a professor of medicine at the Zucker School of Medicine at Hofstra/Northwell and chief of hematology and medical oncology at Lenox Hill Hospital in New York City. “It can lead to a range of emotions like fear, anger, sadness, and uncertainty about the future.”

In this case, it can help to reach out to the following:

• Support Groups Many hospitals and cancer centers have support groups specifically for people with breast cancer. “They offer a safe space to share experiences and gain support from others who face similar challenges,” says Dr. Esteva. For example, the Triple Negative Breast Cancer Patient Support Group from CancerCare offers sessions led by an oncology social worker, and the Triple Negative Breast Cancer Foundation offers virtual support groups and a host of other services.
• Counseling Services Ask your doctor for help finding an oncology social worker to help you and your family navigate the emotional and practical challenges that come with metastatic triple-negative breast cancer, says Esteva.
• Online Communities These communities offer the chance to connect with others who are living with metastatic triple-negative breast cancer, which can help you realize that you aren’t alone, says Esteva. You can visit a virtual triple-negative breast cancer community at Breastcancer.org.