Understanding triple-negative breast cancer and its treatment

There are several breast cancer subtypes. The growth of hormone-dependent breast cancer, the most common subtype, is driven by female hormones. Another common subtype, HER2-positive breast cancer, has excessive copies of a gene called HER2 that makes its cells grow more than they should.

Triple-negative breast cancer, also called basal-like breast cancer, is a subtype that isn't affected by hormones or the HER2 gene. It grows rapidly, is more likely to spread beyond the breast before diagnosis and is more likely to recur than other breast cancers.

Roberto Leon Ferre, M.D., a Mayo Clinic oncologist whose research focuses on triple-negative breast cancer, says recent advances are improving treatment outcomes for people with this disease. "This subtype represents about 15% of all breast cancers," says Dr. Leon Ferre.

Dr. Leon Ferre and other researchers at Mayo Clinic 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. If you've been diagnosed with this breast cancer subtype, here’s what you should know:

What is triple-negative breast cancer?

Roberto Leon Ferre, M.D.

"We do three tests on every breast cancer tumor to help us select treatment: The estrogen receptor, progesterone receptor and HER2. If those three tests are negative, the cancer is considered triple-negative breast cancer," says Dr. Leon Ferre.

Confirming a diagnosis of triple-negative breast cancer starts with a biopsy, a procedure to remove a sample of breast tissue for testing. Your care team will send your tissue to the laboratory for analysis to determine cell type, aggressiveness (grade) and whether the cancer cells have hormone receptors.

Hormone receptors are proteins that can attach to a specific hormone. Some breast cancer cells have receptors for the female hormone estrogen and need it to grow. These breast cancers can be treated with anti-estrogen hormone (endocrine) therapy to block their growth.

The lab will also analyze your cancer cells' genetic makeup to determine if they are HER2-positive or have other tumor markers. HER2-positive cancers have too many copies of the HER2 gene, which causes them to produce too much of the HER2 growth-promoting protein. These breast cancers can be treated with drugs that target the HER2 protein in cancer cells to slow those cells' growth and kill them.

How is triple-negative breast cancer treated?

Dr. Leon Ferre says that for some types of breast cancer, chemotherapy is used after surgery and sometimes not at all. This is not the case for triple-negative breast cancer. "The vast majority of women with this diagnosis will need chemotherapy, and we almost always treat with chemotherapy before surgery," he says.

With other breast cancers, chemotherapy is given after surgery to kill any cancer cells that may have spread beyond the breast.

"Triple-negative breast cancer tends to spread at a microscopic level from the beginning," says Dr. Leon Ferre. This means the cancer must be treated with systemic therapy — a drug or combination of drugs that can be taken orally or through an IV to reach cancer cells in all parts of the body. "The drugs usually used to avoid chemotherapy target estrogen receptors. This cancer doesn't have those, so we rely on chemotherapy, which essentially kills any cell that is dividing rapidly," he says.

Another systemic therapy used to treat triple-negative breast cancer is immunotherapy, drugs that help your immune system identify and kill cancer cells. "At this time, it's the only type of breast cancer for which we use immunotherapy. Of all breast cancer subtypes, it's the one that's better able to alert the immune system to its presence. We can take advantage of that and use medications to activate the immune system further to attack the cancer," says Dr. Leon Ferre.

The immunotherapy approved for the treatment of triple-negative breast cancer is called pembrolizumab. It can be used with chemotherapy or other medicines before surgery and then continued alone after surgery to treat early stage, triple-negative breast cancer at high risk of recurrence. It can also treat triple-negative breast cancer that produces the PD-L1 protein and cannot be surgically removed.

Dr. Leon Ferre says genetic testing can identify additional treatment options for triple-negative breast cancer. "There are some medications that work only in people that have certain genetic mutations, so it's important to ask for genetic testing — even if you don't have a family history of breast cancer."

What should I ask my care team about triple-negative breast cancer?

Before deciding on a treatment plan, Dr. Leon Ferre recommends asking your care team these questions:

• What is the goal of my treatment?
  He says everyone diagnosed with cancer should ask their care team this question. "It's important to know if treatments are likely to cure the cancer or if treatment will be about controlling the cancer."
• Are clinical trials an option?
  If available treatments are unlikely to achieve a cure, consider clinical trials. "There have been many advances in triple-negative breast cancer research, and there are a lot of newer medications that work against this cancer," he says. Participating in a clinical trial may provide treatment options you may not otherwise have.
• Is immunotherapy an option?
  Immunotherapy can treat cancer by blocking immune checkpoints, the part of the immune system that prevents an immune response from being so strong that it destroys a body’s healthy cells. Dr. Leon Ferre says you should ask about immunotherapy if your care team doesn't mention it. Depending on the situation, you may need a test called PD-L1 to decide if immunotherapy would be a good option.
• What are the possible side effects of treatment?
  Before deciding on a treatment plan, it's crucial to understand the side effects of any treatment. "Understanding the potential side effects will help you anticipate how you will feel and prepare beforehand. Every cancer patient should ask about treatment side effects," he says.

Are new treatments being developed for triple-negative breast cancer?

Researchers are studying several new types of immunotherapy with the potential to treat triple-negative breast cancer. "These therapies are promising, and because they work differently than the immunotherapy now available, they are likely to help patients that do not qualify for that drug," says Dr. Leon Ferre. "We also have made progress in a class of drugs called antibody-drug conjugates. These treatments link a small amount of chemotherapy to modified antibodies — naturally occurring proteins that help fight infections. The antibodies have been modified to recognize specific portions of the tumor, instead of bacteria or viruses, and are attached to a small dose of chemotherapy. This allows chemotherapy delivery to tumor cells while sparing cells that aren’t cancerous. These drugs seem to be more potent than traditional chemotherapy."

Researchers have also made advances in the development of targeted therapies for triple-negative breast cancer. These drugs target proteins that control how cancer cells grow, divide and spread. "These treatments are for patients with certain genetic mutations — some targeted therapies specifically block those mutations," says Dr. Leon Ferre. "Some of these drugs are oral and have fewer side effects than traditional chemotherapy. So, we may be able to treat some patients with targeted-drug therapies and perhaps have phases of treatment where they don't need chemotherapy. These drugs can be much better tolerated and usually don't cause nausea or hair loss."

Dr. Leon Ferre and his colleagues at Mayo Clinic are conducting clinical trials of targeted therapies for triple-negative breast cancer. "We're working on ways to identify patients that may do well with less or no chemotherapy. We're finding immune markers that may allow us to identify patients with early stage cancer with such a good prognosis that they may need less intensive chemotherapy."
"We're working on ways to identify patients that may do well with less or no chemotherapy. We're finding immune markers that may allow us to identify patients with early stage cancer with such a good prognosis that they may need less intensive chemotherapy."ROBERTO LEON FERRE, M.D.
If you've been diagnosed with triple-negative breast cancer, Dr. Leon Ferre wants you to know that it's treatable. "It's very sensitive to chemotherapy. With the incorporation of immunotherapy and some newer drugs, we're seeing higher cure rates for patients with early-stage breast cancer. And we have new treatments for patients with metastatic breast cancer. We're making a lot of progress."

This article first appeared on the Mayo Clinic Comprehensive Cancer Center Blog.