This page was reviewed under our medical and editorial policy by
Maurie Markman, MD, President, Medicine & Science
This page was updated on March 2, 2022.
Like the two ends of a magnet, cancer and autoimmunity share a common origin but exert powerful forces that work in opposite directions. Both diseases result from failures in the body’s immune system. Cancer often develops because the immune system fails to do its job in attacking defective cells, allowing the cells to divide and grow. Conversely, an autoimmunity—a faulty immune response that leads to diseases such as colitis and lupus—occurs when the immune system mistakenly attacks healthy cells.
On their own, cancer and autoimmunity often create difficult and challenging circumstances for doctors and patients. In patients diagnosed with either disease, these two opposing forces may collide, further complicating treatments and side-effect management efforts. “There is a definite connection between many autoimmune diseases and cancer,” says Anthony Perre, MD, Internist and Chief of the Division of Outpatient Medicine at City of Hope Atlanta, Chicago and Phoenix. “For example, many autoimmune diseases may lead to inflammation, which has been implicated as a factor in the possible cause of cancer.”
Autoimmune disease and cancer both seek to control the body’s immune system, pushing and pulling immune cells in different directions. For patients diagnosed with both diseases, a medical oncologist acts as a referee to see that neither side of this cellular war has an overwhelming advantage, especially if the cancer treatment involves immunotherapy drugs called checkpoint inhibitors. Patients with autoimmune disease, who already have overactive immune systems, may have difficulty tolerating these immunotherapy drugs, which stimulate immune cells to better recognize and attack cancer.
Since 2011, when the U.S. Food and Drug Administration approved the first checkpoint inhibitor drug ipilimumab (Yervoy®), these immunotherapies have changed the course of cancer treatment for many patients. So far, seven checkpoint inhibitors have been approved to treat a variety of cancers. “We all have an immune system that needs to step on the gas pedal to fight infections quickly when a foreign invader comes in,” says Alan Tan, MD, Clinical Research Medical Director and Medical Oncologist and Hematologist at City of Hope Phoenix. “Immunotherapy fights cancer by releasing the brakes of the immune system and unleashes the power of the immune system to fight cancer cells.”
Immunotherapy may be a safe cancer treatment option for some patients with autoimmune disease, by balancing immune suppressive drugs with immune-stimulating checkpoint inhibitors. “The autoimmune condition can often be managed. And many times, autoimmune adverse events are a good indicator that the immunotherapy is also working to fight the cancer as well,” Dr. Tan says. “As always, weigh the risks and benefits and have a well-informed conversation with your physician.”
Autoimmune disorders generally attack a single organ or part of the body, often causing inflammation in the affected area. While inflammation is not a direct cause of cancer, chronic inflammation may increase cancer risk. Autoimmune diseases that affect the gastrointestinal tract—inflammatory bowel disease, Crohn’s disease and colitis, for instance—cause chronic inflammation in the digestive system that increases the risk of colorectal cancer. Chronic inflammation may damage cell DNA, which may lead to uncontrolled cell growth, one of the hallmarks of cancer.
“Chronic inflammation may also suppress our immune system and affect our ability to repair the damage to our DNA,” Dr. Perre says.
To battle inflammation and limit autoimmune flare-ups, doctors often prescribe drugs called TNF inhibitors, which help reduce inflammation, or an immunosuppressant such as cyclosporin. These drugs are suspected of increasing the risk of multiple cancers. “Treatments that suppress our immune system are commonly used to treat autoimmune disorders, but they may impair our ability to kill cancer cells,” Dr, Perre says. “Some drugs used to treat arthritis and psoriasis may increase a patient’s risk of developing lymphoma.”
Autoimmune disease may also lead to a higher risk of cancers of the blood, bone marrow and lymph nodes, such as leukemia and lymphoma. According to a 2012 study in Haematologica, about 10 percent of all acute myeloid leukemias are thought to be caused by treatments for other conditions, such as chemotherapy and radiotherapy for cancer, or the immune-suppressing drugs that treat autoimmune disease.
Some autoimmune diseases on their own—and not necessarily the drugs to treat them—are associated with a higher risk of acute myeloid leukemia, namely rheumatoid arthritis and ulcerative colitis. Patients whose immune systems aren’t working optimally (whether due to disease or treatment, including those with an autoimmune disease) are thought to have a higher risk of acute leukemia.
The immunosuppressant cyclophosphamide for rheumatoid arthritis has specifically been found to increase the risk for cancers of the blood, bone marrow and lymph nodes, which is one reason why it’s now used less frequently and only for short periods of time in severe cases. Other rheumatoid arthritis drugs, such as azathioprine and methotrexate, have also been linked to lymphoma. Researchers have found that rheumatoid arthritis in the advanced stages puts people at higher risk of lymphoma.
Lupus, rheumatoid arthritis, Crohn’s disease, Graves’ disease/hyperthyroidism and sarcoidosis have been associated with a higher risk of lung cancer. Though researchers have found a link between autoimmune disease and lung cancer risk, it appears that having both an autoimmune disease and lung cancer doesn’t affect overall lung cancer prognosis or survival.
Interestingly, a lower breast cancer risk is associated with some autoimmune diseases, including lupus, rheumatoid arthritis and pernicious anemia (Addison’s anemia). The opposite is true for psoriasis, which is connected to an increased risk of breast cancer. Researchers are still studying why there’s an increased risk of breast cancer in people with psoriasis, but they have ruled out that it’s caused by treatment for the condition.
Muscle-impacting autoimmune diseases polymyositis and dermatomyositis have the strongest connection to an increased risk of bladder cancer. In addition, studies have shown an increased risk of all urological cancers, including bladder, prostate and kidney cancers, in those with an autoimmune disease.
Autoimmune diseases cause a variety of side effects, depending on which organ or body part is affected. Many of the symptoms of these side effects, such as diarrhea, skin rashes, fatigue and bone and joint pain, mirror those that some cancer patients experience due to the disease itself or certain treatments. A patient who has irritable bowel syndrome or Crohn’s disease may already have issues with diarrhea and gastrointestinal distress. Or a patient with lupus or psoriasis may struggle with rashes, itchy skin or bone pain. Chemotherapy or immunotherapy may worsen these symptoms in some patients. “A medical oncologist must balance effectiveness of a treatment against side effects and quality of life,” Dr. Perre says. “There are times when the side effects of treatment may limit the ability to give treatment.”
Doctors and researchers know more than ever about the connection between autoimmune disease and cancer, how to balance treatments and manage side effects. Doctors are also learning more about how to balance the benefits of immunotherapy drugs, which were once off-limits to cancer patients with autoimmune disease. “When checkpoint inhibitors were first being studied, they excluded patients with autoimmune disease, especially if it was active or required suppressive drugs,” Dr. Tan says. “With more experience, we are more comfortable with trying immunotherapy on patients with active autoimmune disease, as long as it is, in general, under control. Patients should talk to their doctor and consider the benefits and risks of doing so.”