Metastatic Triple-Negative Breast Cancer: Emerging Therapies Deliver Hope

One in eight women in the US will receive a breast cancer diagnosis in their lifetime.

There are many different types of breast cancer. The type of breast cancer is often determined by where the cancer started in your breast, if it’s spread.

Metastatic Triple-Negative Breast Cancer

Metastatic Triple-negative is a breast cancer subtype that tests negative for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors 2 (HER2)—receptors commonly found on other breast cancer cells.

Until recently, because most approved therapies that target those three receptors didn’t work, triple-negative breast cancer was difficult to treat.

Metastatic breast cancer means cancer spreads beyond the breast to one or more other areas such as bones or other vital organs, including the liver, lungs, and brain. The tumor divides quickly, grows, and proliferates with a higher chance of metastases, making TNBC extremely aggressive.

Facts About Triple-Negative Breast Cancer

Breast cancer is diagnosed based on the presence or absence of three receptors that drive the development and growth of breast cancer: estrogen, progesterone, and HER2-neu. Triple-negative breast cancer is diagnosed when there is a negative pathology for all three receptors.
Triple-negative breast cancer occurs most often in women ages 40 to 50 (younger than the average age of other forms of breast cancer), African American and Hispanic women, and those with BRCA1 mutations.
Triple-negative breast cancer is more aggressive than other forms of breast cancer, making it more likely to spread to other organs and recur after treatment.
Traditionally, triple-negative breast cancer is typically treated with a combination of therapies, including surgery, radiation therapy, and chemotherapy, but new treatment options such as immunotherapy, PARP inhibitors, and ACD’s are all actively being explored.
Approximately 10-15 percent of breast cancers are triple-negative.

Promising Emerging Therapies

Recently, several new treatment options have become available, and others are on the horizon. New treatments include immunotherapy, PARP inhibitors, and the antibody-drug conjugate Trodelvy (sacituzumab govitecan). In addition, in 2019, atezolizumab, a form of immunotherapy targeting triple-negative breast cancers with PDL1 mutations, was the first approved targeted therapy in metastatic triple-negative breast cancer. Recently, the DESTINY-breast04 trial has had great success with a new antibody-drug conjugate known as trastuzumab deruxtecan. They found that compared to standard chemotherapy, those given the new treatment had about a four month increase in median progression-free survival, as well as a longer overall survival. Their data was recently presented at the 2022 ASCO Annual meeting, and was one of the most promising new therapies featured. A similar study examining an antibody-drug conjugate known as the TROPiCS-2 study, was also featured at the meeting, as were results from a third study, the DetermaIO, which looked at immune checkpoint inhibitors in six cancer types, including triple-negative breast cancer. Researchers are also considering if targeting cancer stem cells, or cancer cells with stem-cell like gene expression would be a viable option. One such study looked specifically at a gene called DOT1L, and used a molecule named EPZ-5676 to inhibit it in different triple-negative breast cancer cell lines and organoid models.

They found that not only did DOT1L act on many cell survival pathways that contributed to the growth of cancer cells, but inhibiting the gene also seemed to inhibit cell and tumor growth. While therapies like these still need to undergo animal and human testing, it’s exciting to see potential new treatment options emerging. Additionally, other types of drugs and regimens are currently being studied, including drugs targeting the PI3K/AKT/mTOR pathway, the androgen receptor pathway, and regimens that combine PARP inhibitors, immune checkpoint inhibitors, and other types of drugs.

As many immunotherapies are still actively being developed and studied, some patients may experience some unexpected side effects from immunotherapies. In order to combat this, ASCO has an informational document for patients which highlights the NCCN guidelines of potential adverse reactions from immunotherapies, and when to be concerned about them. However, if you are experiencing significant side effects or are concerned about the efficacy or safety of a newer treatment, it’s always best to consult your doctor or a medical professional about your concerns, as they will be able to best advise you about your treatment plan. We are always working closely with you, our SBC members and the scientist, researchers, and medical oncologists to advocate and be the voice for our needs and quality of life!