Immunotherapy

Immunotherapy is the use of medicines to help the body’s own immune system recognize and destroy cancer cells. It is a type of biological therapy, which is a class of treatments that use substances from living organisms to fight cancer.

Researchers have long been interested in figuring out how to strengthen the immune system’s ability to fight cancer like it fights other illnesses. Long-term research studies have looked into medicines that can help the immune system better target cancer cells. But it’s only recently that these immunotherapies have started to show signs of success.

Today, immunotherapy is used to treat many different types of cancer, including lung cancer, head and neck cancer, bladder cancer, kidney cancer, and melanoma, among others. Researchers continue to study the use of immunotherapy for breast cancer. As of mid-2022, there is one immunotherapy medicine approved by the U.S. Food and Drug Administration for breast cancer, and a number approved across cancer types for tumors with specific mutations – which in rare situations includes some breast cancers.

How immunotherapy works

The immune system is a complex group of organs and cells that work together to defend the body against bacteria, viruses, and other infectious organisms. Normally, the immune system can tell when cells are harmful to the body. The immune system attacks these harmful cells to prevent you from getting sick.

Yet the immune system can’t heal your body of cancer on its own. Although the immune system can prevent and slow cancer growth, cancer cells often make themselves less visible to the immune system or even interfere with its usual response. Some cancer cells make surface proteins known as immune checkpoints, which are normally used by healthy cells to help the immune system recognize them as a “self” and prevent it from launching a response. With the help of immune checkpoints, cancer cells can also make themselves appear normal to the immune system. This is why some cancers grow, even when a person has a healthy immune system.

Immunotherapies work by making the immune system stronger and helping it see cancer cells with mutations in their cell DNA (or genome) as different from normal, healthy cells without mutation. Once the immune system can recognize those differences, it’s more likely to attack the cancer. Cancers that have the most mutations are considered to have the best chance of responding well to immunotherapy.

Compared to other types of breast cancer, triple-negative breast cancers have the most gene mutations, leading researchers to believe that immunotherapy could have promise for this type of cancer. Also, because these cancers test negative for hormone receptors and HER2 receptors, they don’t respond to treatments that target these characteristics. However, immunotherapies are being tested in other breast cancer subtypes, too.

Who gets immunotherapy

In breast cancer, immunotherapy is typically used in combination with chemotherapy for triple-negative breast cancer. In early-stage breast cancer, it is given before surgery in certain triple-negative breast cancers that are considered at high risk for recurrence. It is also used to treat metastatic or locally advanced triple-negative breast cancer that tests positive for a protein called PD-L1.

The type of immunotherapy usually used in breast cancer is known as an immune checkpoint inhibitor, which works by preventing the cancer cells from disabling the body’s immune response. The cancer cells do this by expressing a protein called PD-L1, which can make them look like normal, healthy cells. The immune cells, known as T-cells, have their own protein called PD-1, which latches on to the PD-L1, and then knows to put the brakes on any attack. As a result, the body’s T-cells do not see the cancer cells as a threat. However, when these checkpoint proteins are blocked by an immunotherapy, the immune cells can recognize the cancer cells as a problem and launch a response.

There is one immunotherapy medicine currently approved by the FDA in the U.S. to treat certain types of breast cancer: pembrolizumab (Keytruda). A second medicine, atezolizumab (Tecentriq), is still being used to treat some people with breast cancer. As of fall 2021, atezolizumab was no longer FDA approved for this use in the U.S., based on clinical trial results that came out after its initial approval. It is not being prescribed to people who have not received it before.

In addition to pembrolizumab, there are a number of immunotherapy medications approved across cancer types but not specifically for breast cancer. An example of such a medicine is dostarlimab-gxly (Jemperli). Note that dostarlimab-gxly has mainly been used for endometrial cancer, and it is still being studied in clinical trials for breast cancer and other types of solid tumors.

Pembrolizumab and dostarlimab-gxly are PD-1 inhibitors, and atezolizumab is a PD-L1 inhibitor. To gain access to these therapies for metastatic breast cancer, a person’s cancer must test positive for PD-L1 or have a high number of DNA mutations, or genetic changes. These changes result in proteins that the immune system might be able to recognize. In early-stage high-risk breast cancer, eligibility for pembrolizumab only is based on features of the cancer, not on PD-L1 status.

Researchers are investigating other types of immunotherapy in clinical trials. To find out if you’re eligible for an immunotherapy clinical trial, visit clinicaltrials.gov and talk to your oncologist.

How immunotherapy is given

Immunotherapy is usually given through a vein every few weeks, and treatment may take a few minutes to a few hours. There are many different forms of immunotherapy, including ones that:

• change a person’s immune cells to help them recognize and attack the tumor—this is the type typically used today in breast cancer
• change the tumor to make it seem more “foreign” which helps the immune cells recognize and attack it

In some cancers, doctors can remove a person’s immune cells and change them genetically, to make those cells better at fighting the cancer. Then the doctors put the changed immune cells back in the person’s bloodstream as a cancer therapy. Right now, this method is only available to treat certain types of blood cancer, but it’s being tested for breast cancer and other cancers. Some clinical trials are also testing whether immunotherapies could be injected directly into the tumor, rather than given via the bloodstream.

Immunotherapy side effects

Immunotherapies help the body attack cancer cells. But sometimes they also cause the body to attack healthy cells because they are stimulating the immune system’s response. This can affect any of the body’s organs and systems, such as the lungs, kidneys, reproductive system, colon, skin, pituitary and adrenal glands, and the thyroid.

Side effects may include fatigue, chills, and body aches; fever; headache; flu-like symptoms; stomach upset; and reactions at the injection site. Your care team can tell you what symptoms to watch for, what to do about them, and when you should call the office. You also will likely need regular lab tests to make sure your organs are functioning normally while on immunotherapy.

Be sure to tell your doctor or your clinical trial’s care team if you already have an autoimmune disorder. You may not be able to receive immunotherapy as a treatment or through a clinical trial. Examples include lupus, inflammatory bowel disease, and rheumatoid arthritis, among others.

Immunotherapies are almost always given with chemotherapy and can lower your white blood cell count, which raises the risk of infection. While you’re on immunotherapy, your doctors will monitor your white blood cell counts and may give you medicine to prevent levels from getting too low. If your counts do get too low, your doctors will recommend you stop immunotherapy treatment for a short period of time or for good.