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Malignancies in lupus demand clinical caution


BUENOS AIRES – Incidences of certain cancers, particularly lymphomas, have been shown to be higher in people with systemic lupus erythematosus, while hormone-influenced breast, ovarian, and endometrial cancers have recently been found to occur less often in SLE patients than in the general population.

At the 10th International Congress on SLE, the researchers responsible for these findings discussed their implications for clinical practice.

Dr. Ann Clarke of McGill University, Montreal, coauthor of a large case-cohort study that found neither immunosuppressant drug use nor disease activity correlated with lymphoma risk as hypothesized (Ann. Rheum. Dis. 2013 Jan. 8 [doi:10.1136/annrheumdis-2012-202099]), said that clinicians should nonetheless consider a history of malignancies when deciding whether to prescribe immunosuppressants.


Dr. Ann Clarke


The study by Dr. Clarke and her colleagues, led by Dr. Sasha Bernatsky of McGill, enrolled 75 SLE patients with lymphoma and 4,961 cancer-free controls with SLE, seeking to determine associations between lymphoma risk and exposures to cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarials, or steroids. The team also looked at Sjögren’s syndrome, disease duration, and disease activity as potential indicators of risk.

Although cyclophosphamide use was seen more frequently among the lymphoma cases (20%) than in the controls (16.8%), this difference did not reach statistical significance. "There isn’t a strong signal that the drugs are responsible," Dr. Clarke said, but she nonetheless argued for caution in the clinic.

"If there is a remote history of malignancy – more than 5 years, certainly more than 10 – I would proceed [with immunosuppressants]," she said. "If there is a recent history, I would try to avoid them, using rituximab or belimumab as appropriate."

Dr. Clarke’s team, again led by Dr. Bernatsky, also conducted research that examined the incidence of specific cancers in an international cohort of 16,409 patients with SLE (J. Autoimmun. 2013 Feb. 11 [doi:10.1016/j.jaut.2012.12.009]).

This study showed that lupus patients had a threefold higher risk for hematological cancers, especially non-Hodgkin’s lymphoma, and a slightly elevated risk for cancer overall, but saw fewer hormone-sensitive cancers than expected, with the standardized incidence ratio of 0.73 for breast cancers (95% confidence interval [CI], 0.61-0.88), 0.44 for endometrial cancers (95% CI, 0.23-0.77), and 0.64 for ovarian cancers (95% CI, 0.34-1.10).

"There certainly seems to be a convincing signal that female hormone-sensitive cancers appear to be decreased in patients with lupus," said Dr. Clarke, who is also codirector of the lupus clinic at Montreal General Hospital. She said that there are various hypotheses as to why, including animal models that suggest that anti-DNA antibodies could have antitumor effects against certain cancer cell lines (Sci. Transl. Med. 2012;4:157ra142).

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