Disclosures: Bernatsky reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
September 30, 2020
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Smoking status, antimalarial use heavily influence cancer risk in SLE

Disclosures: Bernatsky reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Cancers — particularly lung cancer — were more likely to occur among patients with systemic lupus erythematosus who smoked, whereas use of antimalarials was linked to lower cancer risk, researchers noted.

“There is increasing interest in the links between cancer risk and inflammation,” Sasha Bernatsky, MD, PhD, of McGill University in Montreal, told Healio Rheumatology. “In conditions where the immune system is over-active in causing chronic inflammation, like systemic lupus, cancer risk seems to be different compared to people without lupus. Chronic inflammation may be a trigger for cancer — abnormally stimulated lymphocytes from the immune system could turn into lymphoma and scars from inflamed lung could be focal points for lung cancers.”

Lung cancer X-ray
“Our study found lower cancer risk associated with antimalarial drugs — for example, hydroxychloroquine, which is depended upon by the majority of SLE patients,” Sasha Bernatsky, MD, PhD, told Healio Rheumatology. Source: Adobe Stock

“Also, since there are no cures for people with conditions like lupus, we have to use long-term immunosuppressants to keep the immune system under control,” she added. “Many patients are concerned those drugs could themselves cause abnormal cells and eventually, cancer. Sometimes patients even stop taking — or refuse to start — potentially life-saving medications due to this fear of cancer, which has never really been clearly proven. Previous studies of cancer in SLE were limited in that they didn’t necessarily take the entire history of lupus of each patient.”

To examine the risk for cancer among patients with SLE, Bernatsky and colleagues analyzed data from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort, which includes 1,848 patients who met the American College of Rheumatology classification criteria for the disease across 33 centers from 1999 to 2011. Among these enrolled patients, the researchers included and analyzed 1,668 with at least one follow-up visit.

Sasha Bernatsky

Bernatsky and colleagues assessed clinical variables and cancer outcomes among these included patients. Their multivariate hazard regression models — including overall risk and most common cancers — used demographics, smoking status, adjusted mean SLE Disease Activity Index2K and timedependent medications, such as corticosteroids, antimalarial drugs and immunosuppressants.

According to the researchers, 65 cancers occurred through an average of 9 years of follow-up. These included 15 cases of breast cancer, 10 non-melanoma skin cancers, seven lung cancers, six cases of hematological cancer, six prostate cancers, five cases of melanoma, three cervical cancers, three renal cancers, two cases each of gastric, thyroid and head and neck, cancer, and one each of rectal, sarcoma, thymoma and uterine cancers. Among all cancer cases, half occurred in past or current smokers, compared with one-third of patients without cancer.

In their multivariate analysis, the researchers found that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. Smoking was associated with lung cancer. Meanwhile, breast cancer risk was positively associated with age and negatively associated with antimalarial drugs. In addition, antimalarial drugs and higher disease activity were negatively associated with the risk for nonmelanoma skin cancer, whereas age and cyclophosphamide both demonstrated a positive association. Disease activity was associated positively with hematologic cancer risk, but negatively with nonmelanoma skin cancer risk.

“These findings not only help us better understand cancer risk in SLE, but also suggest potential approaches to improve the cancer risk profile in SLE and provide future directions for research,” Bernatsky said. “Our study found lower cancer risk associated with antimalarial drugs — for example, hydroxychloroquine, which is depended upon by the majority of SLE patients. This finding is really novel and many people are interested in our results, because in the general population, it has been shown that hydroxychloroquine may suppress lung cancer cell growth and make cancer more sensitive to chemotherapy.”

“Hydroxychloroquine has even been employed as an adjunct in phase 1 studies of lung cancer therapy, although we still have a lot to learn,” she added. “Even if you are an SLE patient on an antimalarial drug, you should still get cancer screening according to general population guidelines. Though patients sometimes fear their medication may cause cancer, in fact higher disease activity was associated positively with hematologic cancer, suggesting that controlling SLE with medication may potentially improve a lupus patient’s cancer profile.”