Abstract P4-13-07: Meta-analysis of epidemiological studies of Insulin Glargine and Breast Cancer Risk
Authors: Boyle P , Koechlin A , Boniol M , Bota M , Robertson C , Rosenstock J , Bolli GB 
Published: August 2014

Abstract
After having lain dormant for a while, the association between diabetes, its risk factors and treatments, and cancer risk and death is now high on the clinical and research agenda. The microscope is currently focused on the relationships between Pioglitazone and Bladder Cancer, Exenatide and Pancreas Cancer, Liraglutide and pancreas cancer and insulin use and lung cancer. The potential association between use of insulin glargine and breast cancer risk has been the subject of recent major studies.
All data regarding cancer risk and use of insulin glargine has been assembled and meta-analyses performed using state-of-the-art statistical methodology. A random effects model was employed with tests for heterogeneity (I2) and publication bias. These meta-analyses are based on reports from 21 epidemiological studies involving over one million patients and 3 million person-years of observation.
Based on independent estimates from these studies, the Summary Relative Risk (SRR) for all forms of cancer was (SRR = 0.91, 95% CI (0.84, 0.99)), and for breast cancer SRR = 1.11 (95% CI (1.00, 1.48)). For new users of glargine, the SRR for breast cancer was SRR = 1.22 (95% CI (1.00, 1.48)). For colorectal cancer the SRR = 0.83 (95% CI (0.74, 0.94)) and for prostate cancer SRR = 1.14 (95% CI (0.93, 1.39)). Overall, the risk of developing cancer among users of insulin glargine is reduced compared to the risk of users of other insulins. Similarly, the risk of colorectal cancer is reduced among users of glargine.
While the lower bound of the 95% confidence interval is 1.00, the risk of breast cancer does not increase with increasing duration of use of glargine. In some studies the trend in risk with increasing duration of use goes in opposite directions. The development of a detectable breast cancer from the initial carcinogenic event depends on the tumour doubling time. The time for a de novo breast cancer to become detectable ranges from 12.3 years for a doubling time of 150 days; 16.4 years for a doubling time of 200 days; and 20.5 years for a doubling time of 250 days. Most published studies have a maximum of 3–4 years of glargine use.
The databases employed in these analyses were not designed for such epidemiological investigation. A major limitation is the absence of knowledge as to why a potential treatment was prescribed for an individual and why a change in therapy was indicated. Further potential limitations to this meta-analysis include that the comparison group was not the same in all studies but this could also be seen as a strength. The meta-analysis of the randomized trials had several insulin comparators and the retinopathy study had NPH as the comparator. This is not likely to invalidate the findings of this analysis nor would the fact that different adjustments were made in the individual studies.
The current evidence gives no support to the hypothesis that insulin glargine is associated with an increased risk of cancer as compared to other insulins and should give reassurance to physicians and their patients. In respect to breast cancer, there is no indication of a causal association between use of insulin glargine and increased risk of breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-07.