More Evidence Supports the Anticancer Effect of Metformin

Charles Bankhead

October 2012, Vol 3, No 7 - Breast Cancer Symposium

San Francisco, CA—Women with diabetes taking metformin had a significantly lower risk of breast cancer, an association that appeared to grow stronger with increasing duration of follow-up, results of a recent meta-analysis showed.

Overall, metformin users had a 17% lower risk of breast cancer compared with women who did not use the drug, including diabetic women who were taking other hypoglycemic agents. The reduction in risk increased to 25% among women who took metformin for >3 years and to 32% when follow-up started before 1997.

These findings add to some previously reported observational evidence that metformin has a protective effect against invasive breast cancer, according to a study reported at the 2012 Breast Cancer Symposium.

“The finding of a stronger effect size associated with studies of longer duration of metformin use and those that had longer observation periods suggest that the finding may be real,” reported Nananda Col, MD, MPP, MPH, FACP, Professor of Medicine at the College of Osteopathic Medi­cine, University of New England in Biddeford, ME.

“If this result is confirmed in pro­spective studies with a large number of breast cancer events, clinical trials should assess whether metformin can reduce breast cancer risk.”

Obesity and diabetes are risk factors for breast cancer, suggesting a possible association with insulin resistance. Preclinical studies have provided evidence supporting an anticancer effect of metformin that is independent of insulin effects. Additional evidence that metformin has a protective effect against breast cancer has come from several observational studies.

Continuing the examination of the metformin–breast cancer relationship, Dr Col and colleagues conducted a systematic literature review and meta-analysis of published studies. Their analysis included 7 independent studies—4 observational cohorts and 3 case-control studies.

The trials spanned the years 1989 to 2001, and the longest follow-up in any single trial was 21 years. The shortest follow-up was 9 years.

Collectively, the studies included >400,000 adults and 14,000 patients with diabetes. The smallest study had slightly more than 4000 participants, and the largest involved 207,000 adults.

All but 1 of the studies showed a reduced risk ratio for patients taking metformin. The magnitude of reduction across the studies ranged from 5% to 40%. The 1 trial that did not yield a risk ratio <1 demonstrated a neutral effect of metformin (relative risk, 1.02). Of the 7 studies included in the analysis, 4 had confidence intervals (CIs) that included 1.00.

After weighting the studies, the overall adjusted risk ratio was 0.83 (95% CI, 0.71-0.97). Subgroup analyses showed a consistent trend toward lower breast cancer risk in metfor­min users.

An analysis of the studies by year of inception showed that 3 studies beginning after 1996 were associated with an adjusted odds ratio (OR) of 0.95. The 4 studies that began earlier yielded a combined OR of 0.68. Analysis by duration of treatment resulted in an OR of 0.75 for 4 studies whose participants continued taking metformin for >3 years versus 0.94 for 3 studies with a duration of treatment of ≤3 years.

These results are consistent with the results of a recently published analysis involving participants in the Women’s Health Initiative. This analysis yielded a hazard ratio (HR) of 0.75 for breast cancer among women with diabetes who were taking metformin. In contrast, women with diabetes who were taking other antidiabetic drugs had an increased risk of breast cancer, which is reflected in the 1.16 HR for breast cancer risk (Chlebowski RT, et al. J Clin Oncol. 2012;30:2844-2852).