Immune checkpoint inhibitors: Immunotherapy for people with triple-negative breast cancer

By Nicole Brudos Ferrara

Today, treatment for breast cancer is highly personalized to the person diagnosed with the disease and the disease type, including stage and grade, size, and whether the cancer cells are sensitive to hormones. Surgery and radiation are often used as part of treatment, as well as oral or intravenous drugs used to stop the growth of cancer cells in the body and kill them.

Immunotherapy is a type of drug that might be an option if you have triple-negative breast cancer.

Triple-negative breast cancer, also called basal-like breast cancer, is not sensitive to hormones. This means that the breast cancer cells don’t use estrogen or progesterone to grow and they don’t have hormone receptors. This type of breast cancer also doesn’t produce too much of the growth-promoting protein called HER2.

“Triple-negative breast cancer is about 10% to 15% of all breast cancer cases,” says Pooja Advani, M.D., a medical oncologist with the Robert and Monica Jacoby Center for Breast Health at Mayo Clinic  in Florida.

Here’s what people diagnosed with triple-negative breast cancer should know about immunotherapy:

How does immunotherapy work?

Immunotherapy uses your immune system to fight cancer. Your body's disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that blind the immune system cells. Immunotherapy works by interfering with that process.

There are several types of immunotherapy. Immune checkpoint inhibitors are drugs that block immune checkpoints, a part of the immune system whose role is to prevent an immune response from being so strong that it destroys a body’s healthy cells.

"The immune system is a complex network of cells that work well together to identify certain proteins that are present on the surface of cells. These cells recognize these proteins as 'self,' which means a part of our body and not harmful, or 'non self,' which means not a part of our body and potentially harmful," says Dr. Advani. "The job of the immune system is to find and annihilate any attacks on the body. One such attack is cancer cells, which outsmart the immune system. One way they do that is by disabling proteins called immune checkpoints. Certain immunotherapies, called immune checkpoint inhibitors, reverse this process and allow the immune system to effectively attack the tumor cells."

What types of immunotherapy are available for triple-negative breast cancer?

Currently, pembrolizumab is the only immunotherapy approved for the treatment of triple-negative breast cancer. It can be used together with chemotherapy or other cancer medicines before surgery and then continued alone after surgery to treat:

• People with early-stage triple-negative breast cancer who are at high risk of the cancer coming back.
• People with triple-negative breast cancer that has spread or cannot be removed by surgery and whose tumors express a protein called PD-L1.

"Chemotherapy alone for the longest time was the standard of care for this disease," says Dr. Advani. "In both these patient populations, studies have shown that the combination of immunotherapy with chemotherapy is far superior to chemotherapy alone for triple-negative breast cancer. For the patient, it means an improvement in overall survival."

"The use of immunotherapy is one of the real success stories that's moving forward in triple-negative breast cancer right now," agrees Matthew Goetz, M.D., a medical oncologist, co-leader of the Mayo Clinic Comprehensive Cancer Center Women’s Cancer Program and principal investigator of the Mayo Clinic Breast Cancer SPORE.

Does immunotherapy come with side effects?

The most common side effect of immune checkpoint inhibitors, such as pembrolizumab, are rash, diarrhea and fatigue, but side effects vary from person to person.

Side effects that occur with immunotherapy are related to how the immune system responds. "A good analogy is revving up your car engine with your foot on the break, then suddenly releasing your foot off the brake," says Dr. Advani. "That’s exactly what immunotherapy does — it allows the immune system to recognize the tumor, but sometimes that response can be misdirected toward normal tissues."

"A good analogy is revving up your car engine with your foot on the break, then suddenly releasing your foot off the brake. That’s exactly what immunotherapy does — it allows the immune system to recognize the tumor, but sometimes that response can be misdirected toward normal tissues."

Pooja Advani, M.D.

This misdirected immune response can cause inflammation in normal tissues, leading to rarer side effects, such as hepatitis (inflammation of the liver), pneumonitis (inflammation in the lungs) or myocarditis (inflammation of the heart muscle).

"Fortunately, the incidence of these life-threatening complications is relatively low with the type of immunotherapy that is approved for triple-negative breast cancer, but certainly important to know and discuss with your health care professional," says Dr. Advani. "More common side effects are mild flu-like symptoms around the period that patients receive the infusion, including fever, chills, and joint and muscle aches."

Dr. Advani stresses the importance of being vigilant about immune-related side effects. "We are particularly proactive about monitoring the thyroid. We actively check patients' thyroid blood levels while they are receiving immune checkpoint inhibitors, because this type of immunotherapy can impact the thyroid, making it over or under active," she says.

Dr. Advani says other glands that control hormonal functions in the body can be impacted by immunotherapy, so you should make sure your health care professional knows your medical history related to hormone function.

Are there other immunotherapy treatments being developed for breast cancer?

"There are clinical trials actively looking at immunotherapy for patients who have estrogen-receptor-positive disease and patients who have HER2-positive breast cancer," says Dr. Advani.

Dr. Advani hopes research can first expand the number of people with all types of breast cancer who can receive immunotherapy, then expand the types of immunotherapies that can be used beyond immune checkpoint inhibitors.

"One such therapy is CAR-T cell therapy, which has been used in blood cancers, but is now being actively evaluated through clinical trials in solid tumors, such as breast cancer," says Dr. Advani. Vaccines are also being explored, as well as drugs that can be used in combination with immunotherapy that have fewer side effects than chemotherapy. "Work is actively being done to advance the field forward," says Dr. Advani.

Learn more

Learn more about breast cancer and breast cancer types, and find a triple-negative breast cancer clinical trial at Mayo Clinic.

Read these articles:

• "Mayo Clinic Q&A podcast: Surgical options for breast cancer treatment."
• "Using targeted therapy to treat breast cancer."
• "The 4 types of systemic therapy for breast cancer."

Join the Breast Cancer Group on Mayo Clinic Connect.