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Glucagon-like peptide-1 receptor agonists and risk of breast cancer

ARTICLE: Glucagon-like peptide-1 receptor agonists and risk of breast cancer.

AUTHORS: Shari D Bolen and Nisa M Maruthur

JOURNAL: BMJ. 2016 Oct 20;355:i5519. doi: 10.1136/bmj.i5519.

Although many providers and some patients know about the potential risks of pancreatic or thyroid cancer with use of glucagon-like peptide-1 (GLP-1) receptor agonists,1 2 3 risk of breast cancer has also recently arisen as a potential risk with these drugs. The US Federal Drug Administration (FDA) and European Medicines Agency separately conducted pooled analyses of four weight management trials that investigated the use of 3.0 mg liraglutide (a type of GLP-1 receptor agonist).4 5 In these pooled analyses, 12 (0.29%) breast cancer events were reported in the liraglutide arms versus two (0.08%) events in the placebo arms.

Given the rare occurrence of these events, it was unclear whether this difference was due to chance alone or a true increase in breast cancer risk. The LEADER trial (liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results) compared liraglutide at a lower dose of 1.8 mg with placebo, and showed no difference in breast cancer risk.6 However, this study was not designed to analyse breast cancer risk and had too few events for firm conclusions. Although GLP-1 receptors are not found in breast tissue, GLP-1 receptor agonists have been associated with increased expression of fibroblast growth factor, an important growth factor within the breast.7 8 Given the potential concerns regarding breast cancer risk, the FDA suggested additional studies to evaluate this risk.

In a linked paper in The BMJ, Hicks and colleagues (doi:10.1136/bmj.i5340)9 describe an observational study in the UK comparing GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes to further assess breast cancer risk. Although the study included 44 984 patients, the primary analysis focused on only 498 (1.1%) patients taking a GLP-1 receptor agonist and 2422 (5.4%) patients taking a DPP-4 inhibitor. The authors report that use of GLP-1 receptor agonists was not associated with an increased risk of breast cancer overall, compared with DPP-4 inhibitors (4.4 v 3.4 per 1000 person years; hazard ratio 1.40 (95% confidence interval 0.91 to 2.16)). However, when stratified by duration of use, a significant increase in breast cancer risk was identified in patients using GLP-1 receptor agonists for two to three years (2.66 (1.32 to 5.38)). The authors state that the risk diminished at more than three years of use, but the low number of events and people taking GLP-1 receptor agonists at this stage make it difficult to draw any true conclusions for longer follow-up periods.

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Kelsey Bennett