15 Questions - Cancer and Lupus

(September 2012) Cancer risk in lupus is an important topic and these links are an increasing focus in the medical and research community. Many individuals with lupus are concerned about the risk of cancer due to the disease itself or after being treated for many years with immunosuppressive drugs such as Imuran or CellCept. This month, Dr. Sasha Bernatsky answered your questions about lupus and cancer.

1. In general, how much higher is the incidence of cancer in lupus patients than the general population? Holt, MI

The over-all cancer risk in SLE (that is, all cancer types considered together) is only about 10-15% increase compared to the general population. In fact, some cancers are more common in SLE than the general population (for example, lymphoma, a cancer of blood cells), and some cancers are LESS common in SLE than the general population (for example, breast cancer), so it almost evens out, so that over-all, there is only a slight increase in cancer for people with SLE, versus the general population. That’s reassuring, I hope.

2. What are the most common medications used to treat lupus (such as Imuran or CellCept), that can increase the risk of developing cancer? What aspects of lupus/lupus treatments are responsible for an increased risk of cancer with lupus? Oakland, CA

In fact, we do not have much evidence yet that most of the lupus treatments really alter cancer risk. Some doctors actually believe that anti-malarials (e.g. Plaquenil) might even decrease cancer risk, but that has not been completely proven (but is re-assuring). The one drug that we worry most about is cyclophosphamide (Cytoxan), which is not used that often in SLE these days, but it can be a life-saving drug for some people with SLE. Unfortunately this drug is suspected of causing bladder cancer, at least in patients who take the drug for vasculitis. This drug might also be a trigger for some of the hematologic cancers (that is, cancers of blood cells, like lymphoma) that develop in SLE. However, most of the SLE patients who get cyclophosphamide will never get a lymphoma. Thus, if a physician believes cyclophosphamide could save the life of an SLE patient (or, save them from kidney failure), the physician may strongly recommend this drug to certain SLE patients. Our team at the McGill University Health Centre (headed by Lupus Clinic Directors Dr. Ann Clarke and Dr. Christian Pineau) believe that when patients require this drug (relatively few of our patients do), we can potentially limit cancer risk (at least for bladder cancer) by using the drug for as short a period as possible (while achieving disease control), by administering the drug by injection, with lots of hydration, and by using a bladder-protecting drug called MESNA.

3. What types of cancers are most closely attributed to lupus?

We don’t know for sure, but it seems that there are certain hematological cancers (that is, cancers of the blood cells) that are more common in SLE than in the general population, even when these patients have not received immunosuppressive drugs. The strongest association is with certain types of non-Hodgkin’s lymphomas. I would emphasize however, that this is still a relatively rare event in SLE, and occurs in less than 1 in 1000 SLE patients per year.

Also of note, patients with SLE seem to be at more risk for the effects of certain viruses that in the general population can trigger a cancer. To give a specific example, in the general population, human papilloma virus (HPV) can trigger certain gynecological cancers, especially cervical cancer. This is why it is important for women to speak to their treating physician with respect to monitoring for cervical dysplasia, which is a marker for women who have HPV infection, which might later lead to cervical cancer. This is a good strategy for women who want to reduce their risks of cervical cancer.

4. Does the longer your lupus requires immunosuppressive therapy increase your risk of developing cancer? Bloomington, IN

Not necessarily, although there is some debate on the matter. We don’t have good evidence that, in SLE, cancer risk increases with duration of immunosuppressive therapy. In fact, there is a lot of indirect evidence which suggests that, in general, inflammation can promote cancer risk; so, some people think that immunosuppressive medications might actually help decrease the risk of certain cancers. However, that is also a hypothesis that is not really proven. So the bottom line again is that people with SLE should discuss the risks and benefits of drug therapy with their doctor. Certainly, doctors would like to limit the amount of drug that patients receive, to the extent that we can. However, because kidney involvement is so important to treat properly, it is not uncommon for a lupus patient to receive immunosuppressive drugs for several years. Our research concerning cancer risk in SLE has suggested that cancer incidence is spread throughout the duration of SLE, and the relative increase of cancers in SLE, compared to the general population, actually seems to decrease as SLE duration increases.

5. If you have lupus and your white blood cells are "normally" abnormal when you have lab work done, how is cancer detected? Eastampton, NJ

Sometimes cancers have no symptoms until late in their course; so for certain cancers, screening is recommended, to detect cancers in their earliest stages. Breast, colon, and other cancers can be detected by screening (e.g. mammography and colonoscopy). When it comes to lymphoma, there may be symptoms (weight loss, fever, chronically enlarged lymph nodes) which might trigger your physician to ask for the opinion of a hematologist or oncologist. (A sudden or dramatic change in your lab work might also be a trigger for your physician to investigate a cancer.). Not uncommonly for example, a lupus patient will have a lymph node biopsied to make sure that an enlarged lymph node is due to lupus (not cancer).

6. How can a person with lupus reduce their risk for developing cancer? Salt Lake City, UT
One of the most important things in general is to lead a healthy lifestyle…..not smoking, eating a good diet (with lots of anti-oxidants, high fiber, and relatively low fat), exercising, and maintaining a good body weight are all important things that lower one’s risk of many cancers, such as lung cancer, breast cancer, and colon cancer. Additionally, some research suggests that daily low dose aspirin, in the general population, can prevent deaths due to cancer. So, you could discuss with your doctors how they would view adding a low dose daily aspirin to your therapy, in light of your personal health history and the drugs that you currently take.

7. I have "heard" that there is a positive correlation between breast cancer and SLE. My oncologist said, "No”. Has this question been well researched? Huntington Beach, CA

In fact currently we believe that women with SLE have a LOWER risk of breast cancer, over-all, than in the general population. This is ‘on average’…each woman’s personal risk of breast cancer is influenced by several factors, including family history. So, even women with SLE should undergo mammography according to the guidelines that their physicians advise.

8. I have heard differing information about the use of radiation therapy to treat breast cancer in those with SLE. What is the true story

Actually, doctors that use radiation therapy to treat cancer are more concerned about another systemic autoimmune rheumatic disease, which is scleroderma. Scleroderma is a disease that is characterized by a lot of fibrosis (that is, a type of scarring) that occurs in skin and other body systems. Radiation causes some inflammation and sometimes fibrosis in the area of the body that is irradiated. Case reports have suggested that people with scleroderma might be at more risk for fibrosis after radiation. Because some features of SLE and scleroderma are similar, some radiation oncologists are concerned that people with SLE might also have an increased risk of fibrosis after radiation. Some of the best evidence on this subject was published by Veronique Benk and colleagues. Their review suggested that many lupus patients with cancer could have received radiation therapy but only 10% received it, and of this number (four patients) none developed any toxicity. Another more recent study of nine patients also suggested good results. These studies are small and in the end the decision about what kind of therapy a patient should receive for breast cancer depends on the treating physicians.

9. I was diagnosed with lupus 1/2011. I was diagnosed with breast cancer in its advanced stage 7/27/12. The mass has aggressively spread. I am wondering if the reason for the spreading at the rate that it is due to me having lupus and the fact that my immune system is out of whack. Charlotte, NC.

I am sorry to hear of this. As far as I know, there is no conclusive evidence that SLE would cause more advanced breast cancer. SLE is characterized by an over-active immune system, and an active immune system actually has roles in keeping cancer at bay. A lot of scientists are interested in how immune system activity plays a role in cancer initiation and progression.

We did study this question in an earlier study, and we found that women with SLE presented with localized breast cancer 56.2% of the time (nine of 16 cases), compared to the general population of women, where 63.5% of the breast cancers reported are localized. Because of the small numbers in this study, the results are not definitive. It is worth a closer look, and I hope we can tackle that in the future.

10. I have had lupus most of my life. I have a strong family history of various types of cancer. With all the immune suppression drugs I have been on for 30 some years. Are there test I should be getting periodically? Bethlehem, PA

You should undergo cancer screening (mammography, pap tests, colonoscopy, etc.) according to the same guidelines that apply to the general population (based on your family history etc., which you should discuss with our treating physicians)

11. I am in the midst of a large flare and it impacted my kidneys. As a result I am on CellCept. This drug really has not been prescribed long enough to have a track record and/or supporting studies that either link or do not link it to cancer. My kidneys are much healthier right now due to the drug, but I am wondering if the tradeoff is worth taking the drug for 2 years. What are your thoughts on this? Boston, MA

As per my discussion on question 4, we don’t have good evidence that, in SLE, cancer risk increases with duration of immunosuppressive therapy. The bottom line I think is that people with SLE should discuss the risks and benefits of their drug therapies with their doctors. Please don’t stop or reduce the CellCept except on your doctors’ advice.

12. I was diagnosed with leukemia (AML) in 1991 at age 45. Ten years later I was diagnosed with lupus (SLE). I know people with lupus have a higher risk of cancer, but is it possible that there is a connection between my leukemia and lupus? And does my already having had cancer and now having lupus increase my risk of developing cancer again? Suffield, CT

Most of my own research has been on cancers that occur after SLE, but there are plenty of reports of SLE developing after cancer. There are many pathways in the immune system that can lead to both SLE and cancers like leukemias and lymphomas. Your risk of developing a second cancer after a first cancer depends in part on what treatment you had for that cancer, so you should discuss with your oncologist what your risks are.

13. I am currently on 100 mg of Imuran after being on 150 mg. for several years. Is the risk for cancer less with a smaller dosage? Bensalem, PA

Although I don’t have direct evidence that a lower dose of any drug will change your cancer risk, at our center we do try to maintain patients on the lowest dose that is effective in keeping the lupus under control, (and/or tapering completely off, in some but not all cases). This strategy aims to minimize all potential adverse effects of the drug, including for example risk of infection (which may be increased with immunosuppressive drugs).

14. I have been taking CellCept for several years. I have a great concern about cancer. What is my other alternative in regards to immunosuppressive medication? Los Angeles, CA

The treatment of each SLE patient is tailored to the symptoms and disease course. Presumably you are on CellCept for a good reason, such as kidney disease. Please don’t stop or reduce the CellCept except on your doctors’ advice. You should have a serious discussion with your physician to see what your options are. However, at our center we feel fairly strongly that some patients, particularly those with recurrent and/or difficult to treat kidney disease, need to be on drugs like CellCept for several years. As time passes, we hope to learn more about what long-term strategies are best in these cases, but my best advice is to follow the instructions of your doctor in this regard; you can revisit this issue once or twice a year to see if his or her advice has changed on the basis of any new medical research.

On the other hand, while you continue on the prescription medications that your doctors advise, you can also add some ‘complementary’ therapies which may help decrease inflammation in diseases like SLE. For example, there is some evidence that flax seed oil may help patients with SLE, and certain dietary measures (fish oil, turmeric, vegan diets) can help with rheumatoid arthritis and theoretically might also help in some forms of SLE. (But if you take extra supplements like fish oil, please let your specialist doctors know).

15. I have been diagnosed with lupus with an overlap of scleroderma. It has also been said at one point I may even have mixed connective tissue disease. Am I more at risk for cancer because I have more than one connective tissue illness? Elkton, MD

This is a good question, and we don’t know the answer. So far we have only looked at people with SLE who also have Sjögren’s syndrome, and it did not seem that the two conditions in combination dramatically increased cancer risk (above people who have SLE and not Sjögren’s syndrome). Since many believe that inflammatory myositis is associated with cancer risk, then if an SLE patient had an overlap with dermatomyositis or polymyositis, it would be prudent for their physician to think about screening for a few of the more common cancers, like colon and breast. In your own case, with an overlap with scleroderma if you are a woman, I might suggest that you be especially careful to follow guidelines for mammography, since this cancer has been reported to possibly be a bit higher in scleroderma than in the general population. And of course, follow a healthy lifestyle (not smoking, etc.)