In an earlier post on CNiC, we summarized a few studies relating Metformin use to lower risk of cancer (previous post). We have also summarized the enormous range of evidence that overweight and obesity increase risk of cancer (review paper (pdf)).
Now a systemic review of the published literature in the journal Cancer Prevention Research gives strong evidence for consistent findings across studies that metformin reduces risk of cancer onset (incidence) and mortality (study).
What is a systematic review and meta-analysis?
The synthesis of research findings has long been a central part of a research review. It offers the potential to identify areas of agreement in a field and those where the science has discrepancies or require further research (Mosteller and Colditz 1996). Quantitative methods now allow for a number of summary estimates to evaluate the overall benefit (or harm) of a therapy or lifestyle intervention; the level of variation in results between studies; and with regression approaches, one can identify factors that contribute to the variation between studies (Colditz, Berkey et al. 1995). If quality is assessed one can also project how large a benefit (or harm) would be seen if an ideal or prefect study was implemented (Berlin and Colditz 1990). Given the variation in results between studies, we can also project the range of gains or improvements that could be reasonably seen should a program be implemented in a new setting with a defined set of characteristics that were addressed in the earlier collection of research studies.
The systematic review reported in Cancer Prevention Research by DeCensi and colleagues began by searching the medical literature and identifying some 464 publications that addressed metformin and cancer. They applied strict criteria for inclusion in the analysis and extracted results from 11 independent studies that they then analyzed. The studies included a total of 4,042 cases of cancer and 529 deaths. Combining the results from these studies they note that both cancer incidence and cancer mortality are reduced by 30% among users of metformin. These significant benefits overall were also evaluated for subtype of cancer (pancreas, liver, breast, colon, etc). Significant reduction in pancreatic and liver cancer was noted and similar reduction in breast and colon were observed, though the reduction was not statistically significant.
While results showed some variation among studies, the consistent 30 percent reduction in incidence is promising and justifies ongoing efforts to evaluate metformin in randomized controlled trials that will more directly evaluate the potential for metformin to reduce recurrence of breast cancer among 3582 women with stage I and II disease. Details of this trial are reported on the NIH clinical trials web site (link).
In an ongoing randomized clinical trial, we are evaluating weight loss interventions to improve quality of life and reduce risk of recurrence on women with early stage breast cancer (see summary). Just as weight loss sustained over 24 months reduced the risk of progression to diabetes, we will evaluate whether a similar approach can sustain weight loss, improve quality of life, and reduce recurrence of breast cancer.
Other approaches to weight loss in low-income populations also show promise. We have used web tools and telephone based technology to help sustain changes in diet and physical activity among inner city residents in Boston (Greaney, Quintiliani et al. 2009). Results of clinical trials will inform strategies to bring interventions to broader clinical populations, such as through networks of community health centers (see summary).
Berlin, J. and G. Colditz (1990). “A meta-analysis of physical activity in the prevention of coronary heart disease.” Am J Epidemiol 132: 612-628.
Colditz, G. A., C. S. Berkey, et al. (1995). “The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.” Pediatrics 96(1 Pt 1): 29-35.
Greaney, M. L., L. Quintiliani, et al. (2009). “Weight management among patients at community health centers: the Be Fit Be Well study.” Obesity Weight Manageement(October): 218-224.
Mosteller, F. and G. Colditz (1996). “Understanding Research Synthesis (meta-analysis).” Ann Rev Public Health 17: 1-32.