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Pulmonary hypertension (PH) can be caused by several different factors. A person’s risk of developing PH is increased by some types of cancer, certain cancer treatments, and other cancer-related risk factors.
There are five types of PH. Cancer and its treatments have been linked to all five. When one group of researchers studied PH in people with cancer, they found that certain types of PH were more likely to occur:
In some cases, tumors may directly cause PH to develop. In other cases, cancer can cause other health conditions that lead to PH.
Around half of people with lung cancer may have PH. Research shows that lung tumors can rearrange blood vessels and cause inflammation within nearby tissues. These changes may cause narrowing of the blood vessels that connect the heart and the lungs, leading to PH.
PH may be responsible for one common lung cancer symptom called dyspnea (shortness of breath). People with lung cancer who develop PH are more likely to have a poor outlook.
Group 4 PH can develop when a tumor blocks the pulmonary artery (the blood vessel that carries blood from the heart to the lungs). When blood flow becomes partially blocked, the pressure inside the blood vessel rises.
One type of cancer that can block arteries is angiosarcoma. These tumors are formed by the cells that line blood vessels. Another cancer type is intravascular large B-cell lymphoma, which develops when abnormal B cells (a type of white blood cell) grow within blood vessels. Both of these types of cancer are rare.
Cancer often leads to blood clots, which can prevent blood from flowing through veins and arteries. When a person develops serious blood clots, it is known as venous thromboembolism (VTE).
VTEs that occur in the blood vessels of the lungs are called pulmonary embolisms. These conditions can lead to PH. Types of cancer that are most likely to cause VTEs include:
Cancer may lead to pulmonary tumor embolism (PTE) or pulmonary tumor thrombotic microangiopathy (PTTM). In these conditions, tumor cells in one part of the body move into nearby blood vessels and travel throughout the bloodstream to other locations. They then become lodged in the blood vessels of the lungs, forming clumps that prevent blood from flowing normally.
As many as 1 in 4 people with cancer may have PTE, although many don’t have symptoms and are never diagnosed with the condition. PTTM is rarer and more serious than PTE. Both conditions tend to occur alongside adenocarcinoma — a type of cancer that includes liver, kidney, stomach, breast, ovarian, bladder, and lung cancers.
Chronic thromboembolic PH (CTEPH) is a rare type of PH that develops when blood clots form in the blood vessels of the lungs and fail to dissolve. CTEPH causes scar tissue to build up, which may eventually block the blood vessels completely. People with cancer are 3.76 times more likely to develop CTEPH.
Some cancer treatments can increase a person’s risk of developing high blood pressure in the arteries of the lungs. In one study of people who had both cancer and PH, more than 3 out of 5 had undergone cancer treatments within the past three months. Among people in the study with group 1 PAH, researchers estimated that nearly 70 percent had developed the condition because of cancer therapies.
Radiation is a treatment option for several different types of cancer. During radiation therapy, radioactive beams or particles are delivered to a tumor. This treatment often works well to destroy cancer cells, but it may also damage the surrounding healthy tissue.
In some cases, radiation treatments damage blood vessels. This can lead to a condition called pulmonary veno-occlusive disease (PVOD), in which small veins in the lungs become blocked. PVOD is a type of group 1 PAH. People who have undergone radiation treatments sometimes develop PVOD several years later.
Radiation therapy may also lead to heart abnormalities, which could cause group 2 PH. Additionally, people who receive multiple radiation treatments to the chest can develop lung tissue damage, which sometimes leads to group 3 PH.
Many types of cancer are treated with chemotherapy drugs. These drugs often travel within blood vessels throughout the body. They may harm the blood vessels, leading to PVOD.
About 84 percent of people with chemotherapy-related PVOD have used a group of chemotherapy drugs called alkylating agents. These include medications such as:
Other types of chemotherapy may also increase risk. Studies have found that PVOD may develop in people exposed to cytarabine (Cytosar-U), methotrexate (Otrexup), vincristine (Oncovin), doxorubicin (Adriamycin), and other drugs.
Chemotherapy drugs may also damage the heart or lungs, leading to heart failure or lung conditions, which can lead to group 2 or group 3 PH.
Tyrosine kinase inhibitors (TKIs), a form of targeted therapy, are used to halt the growth of cancer cells. TKIs may be recommended for people who have various types of cancer, including chronic myeloid leukemia.
TKIs can increase the chances that a person develops group 1 PAH. However, PAH often goes away once the person stops taking the TKI. Targeted therapies that may increase risk include:
In some cases, PH and cancer may not be directly related to each other. Instead, they may be comorbidities — health conditions that occur at the same time. One condition may cause other comorbidities to develop, or multiple conditions may develop on their own.
Certain risk factors may increase a person’s chances of developing both PH and cancer. Alternatively, a person may be at risk for both conditions due to independent factors.
One risk factor that PH and cancer have in common is older age. PH can occur at any age, but it is more common in older adults. Likewise, a person’s chances of being diagnosed with cancer increase as they age.
Other risk factors that can both increase PH risk as well as raise the risk of certain types of cancer include:
Some people may have risk factors that predispose them to develop PH and separate risk factors that could lead to cancer.
Both conditions can be caused by different sets of gene changes. Some cases of PAH develop due to mutations in a gene called BMPR2.
Cancer can be caused by a wide variety of mutations in other sets of genes. Often, specific gene mutations are linked to specific cancer types. For example, changes in the BRCA genes often lead to breast and ovarian cancers.
Several other PH risk factors can occur separately from cancer. These include:
Likewise, some cancer risk factors don’t have any known connection to PH. Cancer is more likely to develop in people who drink large amounts of alcohol, smoke cigarettes, have come into contact with certain chemicals, or have been exposed to radiation.
On myPHteam, the social network for people with pulmonary hypertension, more than 46,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.
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Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.
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