• Yang Liu, Wei Fan, Hao Chen, and Ming-Xia Yu.
• Center for Nanoscale Characterization and Devices (CNCD), Wuhan National Laboratory for Optoelectronics (WNLO), School of Physics, School of Optical and Electronic Information, Huazhong University of Science and Technology (HUST), Wuhan, China E-mail : dewrosy520@163.com.
• Asian Pac. J. Cancer Prev. 2014 Jan 1; 15 (8): 3403-10.

ContextInterest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA).ObjectivesTo analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs).MethodsA systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-α antagonists with placebo or methotrexate (MTX) (or TNF-α antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNotex6. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies.Results28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-α therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis.ConclusionsThis study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-α antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-α antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.

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