Is Lupus cancer?
No, Lupus and cancer are two distinct conditions with different etiologies, treatment strategies, and prognoses. Although the two may share some general features, such as involvement of the immune system and the importance of gene-environment interactions, the underlying biology and pathogenesis of the two conditions are separate.
Understanding lupus
What is lupus?
Lupus, formally known as systemic lupus erythematosus (SLE), is a chronic autoimmune disease. In individuals with SLE, the immune system mounts an inappropriate response against healthy cells and tissues, causing inflammation and damage to various parts of the body.
The word “systemic” indicates that lupus can affect any part of the body, including the joints, skin, blood vessels, heart, kidneys, lungs, and brain [1]. The disease may range from mild to severe and affects each person differently, based on underlying genetic and environmental factors. However, a majority of patients experience periodic episodes of disease activity, known as flares, followed by periods with no symptoms [2].
Symptoms of lupus
The symptoms of lupus can vary greatly from person to person and may come and go periodically. Common symptoms include:
- fatigue,
- fever,
- joint stiffness, and skin rashes, which emerge due to the underlying autoimmune response.
Other symptoms may include hair loss, dry eyes, mouth ulcers, loss of appetite, nausea, vomiting, diarrhea, weight loss, shortness of breath, joint inflammation, muscle pain, chest pain, and sun sensitivity [1, 2].
One of the most distinctive signs of lupus is a malar rash: a painful and itchy butterfly-shaped rash on the face, which appears on the bridge of the nose and spreads out over the cheeks [2]. However, only about 30% of patients with lupus present with a malar rash [3]. More serious symptoms can include gastrointestinal problems, pulmonary issues, kidney inflammation, thyroid problems, osteoporosis, anemia, and seizures [3].
Causes and risk factors for lupus
Like many autoimmune disorders, lupus most likely results due to a combination of genetic and environmental triggers. However, the exact cause(s) of the disease remain unknown. Current evidence suggests that particular genetic variants, hormonal imbalances, and environmental exposures may all be associated with increased incidence of lupus. To date, over 50 genes associated with lupus have been identified. Moreover, having a family history of lupus (or of other autoimmune conditions) may elevate an individual’s risk of developing SLE [4]. These findings suggest that there is a genetic component underlying lupus in some individuals with the condition.
Environmental factors may also play a role in the onset of lupus in susceptible individuals. For example, triggers such as smoking, stress, certain antibiotics, ultraviolet radiation, and exposure to toxins like silica dust have been identified as potential contributors to lupus [4]. Lastly, there is some evidence that hormonal imbalances may be implicated in lupus. Lupus affects disproportionately more women than men, with 9 out of 10 cases occurring in females [4]. Additionally, many women with lupus experience symptom flares just before menstruation and during pregnancy, when estrogen levels are relatively high [4]. These findings suggest that hormones such as estrogen may play a role in the pathogenesis of SLE.
When it comes to risk of developing SLE, certain groups appear more vulnerable to the disease. Statistically, women are more likely to develop lupus than men, although the disease sometimes presents more severely in men. Lupus also tends to be diagnosed more frequently in young adults (aged 15-44) compared to children or elderly individuals [4]. Within the United States, lupus appears more commonly among African Americans, Hispanic / Latino People, Asian Americans, Native Hawaiians, and Pacific Islanders compared to Caucasian individuals [4].
Understanding cancer
What is cancer?
Cancer is a complex set of diseases characterized by the uncontrolled growth and division of cells in the body. Normally, cells multiply and divide in a controlled manner, replacing old cells as they die. However, sometimes this process goes awry, leading to the formation of superfluous cells that can develop into a mass called a tumor. These tumors can be benign (non-cancerous) or malignant (cancerous), with the latter having the capacity to invade nearby tissues and spread to other parts of the body in a process called metastasis [5].
Types of cancer
It is crucial to understand that cancer is not a single disease, but a collection of related diseases, all of which are linked by uncontrolled cellular proliferation. There are over 100 different types of cancer, most of which are named after their tissue of origin. For instance, lung cancer starts in the lung, and breast cancer starts in the breast [5]. However, cancers that arise from the same tissue type can be very different from one another. For instance, two cases of breast cancer can differ significantly in their genetic profiles and the composition of cells present within the tumor microenvironment [6]. These factors help determine the severity and treatability of disease.
There are several general types of cancer, which are classified according to the type of tissue that is affected [7]:
- Carcinoma: cancers of epithelial origin (i.e., those that start in the skin or in other tissues which line the surfaces of organs and cavities).
- Sarcoma: cancers of connective tissues (e.g., cartilage, muscles, bones, and blood vessels).
- Leukemia: cancers of the bone marrow, which produces blood cells.
- Lymphoma and myeloma: cancers of the immune system (lymphoid and myeloid cells, respectively).
Symptoms of cancer
The symptoms of cancer vary widely depending on the type of cancer and stage of disease. For example, breast cancer is often identified due to a painful lump in the breast tissue, whereas leukemias may be first noticed due to abnormal bruising and bleeding. However, some “warning signs” occur commonly across various forms of cancer, including [8]:
- Fatigue
- Fever
- Heavy night sweats
- Unexplainable aches and pains
- Unexplainable weight loss
- Unusual lumps or swellings anywhere on the body
- Changes in appetite
- GI disturbances and changes in bowel habits
- Unexplainable bleeding or bruising
Many of these symptoms are quite general and can be caused by other conditions or disorders. However, if such symptoms are experienced in combination and do not seem to resolve on their own, there may be a more serious underlying condition at play.
Causes and risk factors for cancer
Because there are so many individual types of cancer, it is impossible to identify a singular or definitive set of causes. Cancer is a multifactorial condition, meaning that it usually emerges due to a combination of contributing causes. Most often, cancer results due to an interaction between genetics and environmental factors. Mutations in genes which regulate the cell cycle—such as proto-oncogenes, tumor suppressor genes, apoptotic genes, and DNA repair genes—are seen in many cancers [6]. Such mutations may be inherited or induced by environmental insults, such as exposure to carcinogenic compounds, chronic inflammation, and immune dysregulation [9]. Cancer can also be caused by certain viral infections that spur excessive cellular proliferation (for example, human papillomavirus (HPV) and cervical cancer). Major risk factors for cancer include a family history of disease, tobacco use, exposure to UV light, environmental pollution, alcohol consumption, obesity, stress, and viral infections [9].
What are the main causes and risk factors for cancer?
The main causes and risk factors for cancer include tobacco use, which accounts for 20-30% of all cancer cases, and obesity, associated with another 30% of cases. Other significant factors include unhealthy diet, lack of physical activity, exposure to certain infections, and age, as the risk generally increases until 70-80 years old. Environmental factors are implicated in about 80% of all cancers. It's important to note that the impact of specific factors can vary greatly depending on the type of cancer [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37].
Key differences between lupus and cancer
Underlying biology
Lupus is an autoimmune condition, meaning that it develops due to a misguided immune response against healthy tissues. The disease is characterized by the production of antinuclear antibodies (ANAs) and the synthesis of autoantibodies that recognize components of the cell nucleus [10, 11]. In lupus, B cells are hyperactive to various stimuli, leading to an overproduction of immunoglobulins and autoantibodies. These autoantibodies can form immune complexes with endogenous cell proteins, which promotes pathogenesis by stimulating inflammatory cytokine production and immune cell activation [12].
Cancer, on the other hand, is not an autoimmune condition. It is a set of diverse diseases that result due to excessive and dysregulated cellular proliferation. It is driven by a series of accumulating genetic and epigenetic changes influenced by hereditary factors and the somatic environment, which provide cancerous cells with a survival advantage over surrounding normal cells [13]. Rather than triggering an “anti-self” immune response, cancer cells often evade immune recognition and develop resistance strategies to avoid elimination.
Treatment
Lupus and cancer have very different biological underpinnings, and thus necessitate distinct forms of treatment. While there is currently no cure for either disease, several treatment modalities are used to prevent progression and reduce disease-related complications.
Treatment options for lupus include:
- Antimalarial drugs. Antimalarial drugs are the first-line treatment for lupus. The main type of antimalarial drug used for lupus is hydroxychloroquine. This drug works by reducing the levels of inflammation and autoantibodies in the body, which can help with lupus symptoms like pain and swelling. It can also improve lupus skin symptoms, reduce lupus flares, prevent organ damage and complications, and improve survival [14].
- Immunosuppressive drugs. Immunosuppressive medications are another common treatment for lupus. These drugs lower the body's immune response to control inflammation. Examples of such medications include mycophenolate mofetil and cyclophosphamide [15].
- Biologics. Biologic medications, such as monoclonal antibodies, are sometimes used in the treatment of lupus. For example, belimumab is a well-established add-on treatment that can improve joint manifestations, skin symptoms, and fatigue, and reduce severe flares and steroid use. Anifrolumab is a newer treatment that has shown positive results in recent studies [16, 17].
- Corticosteroids. Corticosteroids are often used to reduce inflammation and control pain in lupus patients. They may also help prevent or reduce lupus flares [18].
Treatment options for cancer include [7]:
- Surgery. Surgery is a common treatment option for solid tumors, aiming to remove as much of the cancer as possible. Surgery is often used in combination with other therapies to promote the eradication of as many cancer cells as possible.
- Chemotherapy. Chemotherapy involves the use of medications that are toxic to rapidly dividing cells. This approach may be used to reduce the size of a tumor or lower the number of cancer cells in the body, thereby reducing the chances that the cancer will metastasize to other body sites. However, chemotherapy can also kill non-cancerous cells which divide quickly, such as skin, hair, and blood cells.
- Radiation therapy. Radiation therapy uses high-power, focused beams of radiation energy to damage DNA and kill cancer cells. This can be done inside the body (brachytherapy) or outside the body (external beam radiation).
- Immunotherapy. Immunotherapy leverages the body's immune system to recognize and eliminate cancer cells. These therapies aim to boost immune recognition of cancer-associated antigens, thereby enabling the body's natural defenses to eradicate the cancer cells.
- Targeted drug therapy. Targeted drug therapy uses small compounds that interfere with specific molecules or receptors that help cancer cells grow and survive.
Prognosis and survival
Lupus and cancer also differ in their prognosis and survival statistics. Survival rates for lupus patients can vary depending on several factors, including the severity of the disease and the patient's demographic characteristics. However, one study [19] reported that the survival rate of selected patients from the time of SLE onset was 93% at 1 year, 73% at 5 years, and 60% at 10 years. A separate study [20] reported survival rates at 5, 10, and 15 years after diagnosis to be 96%, 93%, and 76%, respectively. Furthermore, there is evidence that gender may play a role in lupus survival rates. In a study of 110 patients with SLE, 87% were still alive after 10 years; however, the cumulative survival for men was 69%, while for women it was 90% [21]. Patients who have developed lupus nephritis—i.e., kidney failure due to targeting by anti-renal autoantibodies—generally have the poorest prognosis and survival rates.
Cancer prognosis and survival rates can also be quite varied and depend on factors such as the type of cancer, stage of disease progression, and presence of other health conditions or comorbidities. Additionally, the presence of metastases, levels of certain biomarkers in the blood or tumor sample, and the patient’s age may help predict chances of survival and recovery. Due to this heterogeneity, it is not possible to give an overall survival rate or prognosis for all cancers. However, some studies dealing with particular types or subtypes of cancer have identified useful prognostic markers. In non-small cell lung cancer, for example, relevant prognostic factors include patient age, serum albumin levels, serum LDH levels, pulmonary dysfunction, and lung performance status [22]. In breast cancer, on the other hand, tumor size, nodal status, and grade are the most important prognostic factors for long-term survival, with 10-year survivors showing a 90% 5-year relative survival rate [23]. When dealing with metastatic breast cancer in particular, significant prognostic factors include metastatic-free interval, localization of metastases, and hormone receptor status [23].
Overall, the prognosis and survival associated with both diseases varies according to a number of biological and demographic parameters. While lupus and cancer can be fatal in some cases, many cases are treatable and can be managed with appropriate medical care. Therefore, when discussing the prognosis or survival rates of these diseases, it is crucial to consider details such as disease stage, patient characteristics, and genetics (among other factors) and avoid overgeneralized claims.
Conclusion: lupus is not a form of cancer.
Lupus and cancer are two distinct conditions with different etiologies, treatment strategies, and prognoses. Although the two may share some general features, such as involvement of the immune system and the importance of gene-environment interactions, the underlying biology and pathogenesis of the two conditions are separate. In lupus, hyperreactive B cells become stimulated to produce autoantibodies against various self-antigens. This leads to inflammation and destruction of various healthy tissues, including the joints, skin, hair, blood vessels, neural tissue, and kidneys. Cancer is characterized by unregulated cell division and proliferation, leading to the formation of neoplasms. Cancer is not an autoimmune condition; in fact, cancer cells often develop mechanisms to evade detection by the body’s immune system. Given these differences, treatment strategies for lupus and cancer differ significantly. Treatments for lupus generally focus on reducing inflammation in order to limit tissue damage and dampen the autoimmune response. Conversely, cancer treatments may aim to boost the patient’s immune response against cancerous cells to facilitate targeted elimination. Other methods for eliminating cancerous cells include surgery, chemotherapy, radiation, and small-molecule inhibitors.
Despite the differences between these two conditions, many individuals confuse lupus as a type of cancer or believe that lupus can cause cancer. Why is this the case? One reason might be overlapping symptoms between lupus and certain types of cancer, such as lymphomas. Because both conditions involve the immune system, they may present shared symptoms such as fever and swollen lymph nodes [24]. Occasionally, blood tests may show similar elevations in white blood cell counts in patients with lupus and lymphomas, which may further contribute to confusion in distinguishing the two conditions [25]. Lastly, there is some evidence suggesting a statistical association between lupus incidence and development of lymphoma [26]. This finding may lead some to speculate that lupus increases an individual’s risk of developing certain lymphomas. However, it is important to note that correlation does not imply causation, and further research is needed to determine whether there are shared biological mechanisms linking lupus to various lymphomas.
Why do some people confuse lupus with cancer?
Lupus and certain types of cancer, such as lymphoma, can share similar symptoms, which can lead to confusion in diagnosis. Both conditions affect the immune system and can present with symptoms like fever and swollen lymph nodes. Even blood tests can reveal similar findings for lupus and early lymphoma. Lupus, in particular, is sometimes referred to as "the great imitator" because its symptoms can mimic many other conditions, making diagnosis challenging. In fact, a 2021 study found that the average time to arrive at a lupus diagnosis was almost 4 years [27].
Can lupus be misdiagnosed as lymphoma?
Yes, lupus can sometimes be misdiagnosed as lymphoma. This is because lupus and lymphoma share common symptoms such as fever and swollen lymph nodes. Even blood tests can reveal similar findings for lupus and early lymphoma. To confirm the presence of lymphoma cells, doctors may order a lymph node biopsy or peripheral blood smear. Lupus is sometimes referred to as "the great imitator" because its symptoms can mimic many other conditions, making diagnosis challenging. However, it's less common for doctors to misdiagnose lupus as lymphoma [27].