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Myositis and Cancer: Quantifying the Link


Patients with dermatomyositis (DM) who were positive for a specific antibody — anti-transcriptional intermediary factor 1 (anti-TIF1) — were at more than threefold increased risk for cancer, a retrospective U.K. study found.

In a cohort of 263 DM patients followed for a median of 11 years, 38% of patients who were anti-TIF1 antibody positive had developed cancer compared with 15% of those who were anti-TIF1 negative, according to Alexander Oldroyd, MBBS, of the University of Manchester, and colleagues.

Accordingly, the hazard ratio for the antibody-positive group was 3.4 (95% CI 2.2-5.4), the researchers reported online in Rheumatology.

Dermatomyositis belongs to the group of disorders known as the idiopathic inflammatory myopathies, which are characterized by muscle inflammation and weakness as well as circulating antibodies. Previous studies have identified a strong association between DM and cancer, with one meta-analysis finding a fivefold higher risk compared with the general population.

The anti-TIF1 antibody is DM-specific and confers an even higher risk, which has been estimated at 38-71% within 3 years before or after DM onset. Longer-term risks, however, have not been established, so the researchers analyzed data from the U.K. Myositis Network for patients followed for at least 10 years to determine risks, ages at cancer development, and types of cancer. “Further knowledge of the longer-term risk of cancer, common sites of malignancy, and age association would usefully inform cancer screening strategies and optimize patient management,” Oldroyd and colleagues wrote.

Patients were recruited from 74 centers throughout the U.K. Data about demographics and clinical patterns were collected, and all participants had blood samples taken to detect various antibodies, including anti-Jo-1, anti-PL7, anti-PL12, anti-PM-Scl, and anti-TIF1.

A total of 55 patients were anti-TIF1 antibody positive, and 208 were negative. The majority were women, and median age at DM diagnosis was 47.

Cancer developed within 3 years prior to DM onset in 13% of the anti-TIF1 positive group compared with only 4% of the negative group (P<0.01), while the malignancy was detected within the 3 years after DM diagnosis in 26% vs 6%, respectively (P<0.01).

In the antibody-positive group, all cancers diagnosed after DM onset occurred within 2.5 years, and no cases were reported during the remainder of the 10-year follow-up. In contrast, cancers continued to be detected throughout the study period for the anti-TIF1 negative group, reaching 9.8% by 5 years, 11.7% by 7.5 years, and 14.1% by 10 years.

Among the anti-TIF1 positive patients, none of those who were younger than 39 at the time of DM diagnosis developed cancer, while 53% of those who were 39 or older at onset of DM subsequently were diagnosed with cancer (HR 4.1, 95% CI 2.5-6.7). This observation suggests that heightened screening for cancer in patients who are anti-TIF1 positive should begin at age 39, according to the authors.

In the anti-TIF1 positive group, the most common types of malignancy were breast cancer (33%), ovarian cancer (19%), and lymphoma (14%). In the anti-TIF1 negative group, the most common were breast cancer (25%), lymphoma (13%), and bowel cancer (13%). Ovarian cancer was markedly higher in the anti-TIF1 positive group (19% vs 2%, P<0.05).

Previous studies have noted the increased risk for ovarian cancer among women with DM, but this is the first study to determine that the risk was primarily among the anti-TIF1 positive group, “suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1 antibodies. Clinicians should therefore apply increased vigilance for potential ovarian pathology in anti-TIF1 antibody positive cases,” the researchers wrote.

“Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer,” the team concluded.

Limitations of the study, Oldroyd and co-authors said, include the possibility of survival bias and uncertainty about the time of DM onset in some cases.

The study received research support from the National Institute for Health Research.

The authors reported no conflicts of interest.


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