By Maxine Lipner
Published on August 18, 2023
Medically reviewed by Doru Paul, MD
Immunotherapy can boost your body's immune response to cancer cells and hopefully kill them.1 For those with triple-negative breast cancer, immunotherapy can make a difference.
This is a type of breast cancer in which the malignant cells don't have either estrogen or progesterone receptors and also don't make too much human epidermal growth factor receptor 2 (HER2) protein (which can cause cancer cells to grow more rapidly).2
In this article, you'll learn when immunotherapy can be used for breast cancer, what effect this has on tumors, types of immunotherapy, potential side effects, and more.
Elvira Zhuravleva / Getty Images
Goals of Immunotherapy for Breast Cancer
Immunotherapy aims to get the immune system to recognize and destroy breast cancer cells. The body has a checkpoint system where proteins on immune cells must be turned on or off to mount an immune response.1 This helps keep the immune system from attacking normal cells.
Some cancer cells develop these checkpoint proteins to hide themselves from the immune system. Drugs can be used to circumvent the checkpoint system so the immune system can attack the cancer cells. These are known as checkpoint inhibitors.1
Stages and Types of Breast Cancer
Immunotherapy medication can be effective for certain types of breast cancer when given at the right stage.
To help the immune system battle breast cancer, checkpoint inhibitors target an immune system protein known as PD-1, which is located on T cells (a type of immune system white blood cell). This protein binds to the PD-L1 protein on normal cells, keeping the T cell from attacking them. Some breast cancer tumor cells produce PD-L1, reducing attack by T cells.3
A checkpoint-inhibiting drug such as Keytruda (pembrolizumab) can target the PD-1 protein present on the immune cells and blocks the interaction with PD-L1 molecules present on the cancer cells.
By inhibiting this interaction, this medication releases the brake placed on the immune system by the tumor cells and allows the immune system to work to its fullest in attacking breast cancer.
Keytruda has Food and Drug Administration (FDA) approval to treat triple-negative breast cancer.4 It is approved for use with chemotherapy to treat breast cancer in cases where the PD-L1 protein is found on the tumor cells. Without the PD-L1 present on the tumor cells, this treatment will, unfortunately, not work.
Those eligible for this approach are:1
People with stage 2 cancer, in which the tumor has grown a little and spread to a few nearby lymph nodes, or stage 3, in which the tumor is bigger than in stage 2 and has spread to even more lymph nodes, are good candidates. Here, immunotherapy can be used before the tumor is surgically removed and after.
The tumor has returned after treatment and is still local but can't be removed surgically.
The cancer is no longer just in the breast. It has spread elsewhere in the body.
Immunotherapy Effect on Breast Cancer Life Expectancy
In the past, surgery alone was thought to be the cure for breast cancer. But even with whole breast removal, most people did not fare well. That's because, despite its location within the breast, breast cancer is thought to be a systemic problem.
While immunotherapy had made inroads in the treatment of melanoma and lung cancer, initial studies were not very promising for immunotherapy, like checkpoint inhibitors alone for triple-negative breast cancer. Investigators found that without any preselection, response to this kind of therapy was seen in less than 10% of cases.5
But when treatment with immunotherapy (such as Keytruda) was given only to those with a specific type of triple-negative breast cancer and chemotherapy (chemo) was also given to help enhance the treatment, outcomes improved.
When people with advanced triple-negative breast cancer with high levels of PD-L1 were treated with both chemo and immunotherapy, they were found to have an overall survival of 23 months. When chemotherapy alone was given, survival was only 16.1 months. The combined approach improves outcomes for people with this type of breast cancer.6
Types of Breast Cancer Immunotherapy
The theory of harnessing the body's own immune system has been gaining traction. While the checkpoint inhibitor is the only approved immunotherapy agent for breast cancer, other approaches are also being tried, such as the following.
Cancer Vaccines
Breast cancer vaccines are being tested, with the anticipation that the vaccine will prime the immune system to recognize and target the cancer. Potentially, these could work to:7
Keep breast cancer from recurring once you've been in remission for some time
Mop up any remaining cancer cells that are lingering after treatment
Ensure a current tumor doesn't get any larger or spread elsewhere
Cancer vaccines could work because there are substances on the surface of the cells known as antigens that the body recognizes as harmful. The antigens are specific to certain cancer cells and not found in healthy ones. The vaccine trains the immune system to seek out the antigens and destroy the cancer cells.
A database from the National Center for Biotechnology Innovation lists clinical trials you may be eligible to participate in.
T-Cell Transfer Therapy
With this approach, your own T cells are harvested and transferred back into your body.8 This can be done in one of two ways. One is by using tumor-infiltrating lymphocytes (TIL). The other is by using chimeric antigen receptor (CAR) T-cell therapy. These therapies have not been approved for use in breast cancer patients and are still experimental.
With TIL therapy, the immune cells that have penetrated the area of the tumor are believed to be best able to recognize the cancer cells and kill them. But more of them are needed to effectively attack the tumor.
An oncologist (cancer specialist) will remove some of your T cells to be tested to determine which has the most robust response to your tumor. The next step is to put these into a substance that allows the chosen T cells to replicate quickly and then put these cells back into the body so they can effectively battle the tumor.
Akin to TIL therapy, with CAR T-cell therapy, these same T cells are altered in the lab. They are modified to make the CAR protein, which enables them to attach to the surface of cancer cells and more effectively attack them. These modified cells are then returned to the body.8
Monoclonal Antibodies
When faced with an infection or other foreign invader, our bodies make substances known as antibodies to fight the infection. Antibodies attach to an antigen on the invader. Once they have latched on, they can call on other parts of the immune system to find and destroy the invader.
It's possible for researchers to make monoclonal antibodies in the lab that target a specific cancer antigen. These can be used in some cases to make the immune system work better in finding and battling cancer. Here are some of the ways monoclonal antibodies can help the immune system to do its job better:9
They can serve as a marker for the immune system by attaching to the cancer cells and effectively sending up a flare where the cancer is located. This allows the body's own antibodies to come and destroy the tumor.
Other monoclonal antibodies (such as Keytruda) work to target immune system checkpoints, blocking these so the immune system can attack the cancer in full force.
Some monoclonal antibodies can block antigens that help cancer cells to grow and spread, like the HER2 protein found in some breast tumors. The monoclonal antibody Herceptin (trastuzumab) can work by latching on to these proteins and keeping them from becoming active.
Other New Breast Cancer Treatments
Immunotherapy is not the only new option for treating breast cancer. Others include:10
Antibody-drug conjugates: A monoclonal antibody latches onto the cancer and delivers a payload of chemotherapy to kill the cancer.
Kinase inhibitors: HER2 is a type of kinase protein. Cells rely on kinases to signal them to grow. Meanwhile, kinase inhibitors block these kinases and help keep cancer from growing.
Hormonal therapy: Some breast cancers have estrogen and/or progesterone receptors that enable the cancer to grow. There are now drugs to block these receptors and keep the cancer in check.
Side Effects of Immunotherapy
While immunotherapy can be an excellent option in treating breast cancer, there can be a downside. Some people may experience uncomfortable side effects, such as the following:1
Tiredness
Nausea
Diminished appetite
Cough
Rash
Constipation
Diarrhea
In some cases, people have a reaction while receiving the immunotherapy transfusion. You may feel your face flush, and you may experience other telltale signs. Your skin may become itchy, you may become dizzy, develop a fever, and even have trouble breathing. If having this kind of reaction, be sure to alert the person administering the medicine right away.
Immunotherapy Side Effects: What to Know
Preexisting Conditions
Immunotherapy may not be the right choice for everyone. For those with autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, or lupus, the use of immunotherapy may be trickier. That's because, in these conditions, the immune system reacts against the body's own healthy tissue.
When using immunotherapy such as a checkpoint inhibitor, which causes the immune system to ramp up instead of attacking the cancer alone, the immune system may also go after otherwise healthy organs. If the immune system starts attacking your lungs, liver, kidneys, and other essential tissues and organs, this can become life-threatening.
What Happens During Immunotherapy for Breast Cancer
With immunotherapy for breast cancer, the idea is to rely on the power of your immune system to target breast cancer tumors. As part of the process, your oncologist will likely test your tumor to see if it may be responsive to current immunotherapy.
Before giving a medication such as Keytruda, they will look to see whether there are PD-L1 proteins on the cancer cells that your immune system can target.
If these proteins are present, you will likely be a good candidate. You can expect to receive the medication via an intravenous infusion every three to six weeks, depending on your needs.1
Self-Care on Immunotherapy
It's important to keep other aspects of your health in mind when going through immunotherapy. Here are some ways to help boost your emotional health during this period:11
Engage in activities that make you happy: Your list will be personal to you but may include things such as taking a walk in nature, spending an afternoon with a close friend, rereading your favorite book, or taking a yoga class.
Prioritize rest: This means making sure you get lots of sleep. If stress is interfering with getting to sleep or staying asleep, discuss this with your healthcare provider, who may be able to prescribe medication to help.
Let people know what you need: During your treatment, you may need help completing your usual chores. Make a list of things that others can do to help, and don't be afraid to ask. This may mean a school pickup, help with preparing dinner, a ride to and from treatment, or any number of other things.
Questions for Your Oncologist
You can expect to periodically meet with your oncologist while undergoing immunotherapy for your breast cancer. When you do, it's best if you come prepared. Here are some questions to keep in mind:12
Will immunotherapy put me at risk for other infections?
Do I need to discontinue any medications?
Is bleeding an issue here? If so, what should I do if I get cut?
Do I need to worry about stomach issues like nausea and diarrhea?
What should I do if I develop a rash?
What should I do if the treatment makes me itchy?
Do I need to avoid the sun?
How can I overcome fatigue?
Are there any supplements I should be taking?
When is it important for me to call you?
Summary
Immunotherapy helps to boost the immune system and can be a valuable tool for fighting some types of breast cancer. In the case of triple-negative breast cancer, there is an approved immunotherapy medication that can help in some cases.
Other immunotherapy approaches being studied, such as vaccines, T-cell transfer therapy, and monoclonal antibodies. But immunotherapy breast cancer treatment is not for everybody. To benefit, you must have the right type of tumor and also not have preexisting immune conditions that may be triggered.
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