Metformin as an Adjuvant Treatment for Endometrial Cancer?

Steven Fox

April 08, 2011

April 8, 2010 — The oral diabetes drug metformin could potentially play a role as an adjuvant treatment in the management of endometrial cancer, according to results from an in vitro study carried out in England.

Writing in the March issue of the Journal of Clinical Endocrinology and Metabolism, Bee K. Tan, MBBS, PhD, MRCOG, MRCPS (Glasg), from the University of Warwick, Coventry, and colleagues explained their rationale for pursuing this line of research.

"Insulin sensitizers, in particular, the biguanide metformin, are widely used in the management of women with polycystic ovary syndrome (PCOS). Metformin not only ameliorates insulin resistance and hyperinsulinemia in PCOS women, but also its long-term use improves ovulation and menstrual cycle regularity," the authors write.

In addition to suppressing glucose production in the liver, metformin has demonstrated beneficial effects in other types of tissues, including adipose tissue, skeletal muscle, and the vascular endothelium. More recently, the drug has also been shown to inhibit the growth of breast cancer cells.

Because women with insulin-resistant states are more likely to develop endometrial cancer, the researchers decided to use various assays to study the invasive qualities of lab-obtained human endometrial cancer cells (ECC-1) in sera samples obtained from a cohort of 21 women both before and after they had undergone a 6-month course of metformin (850 mg twice daily). Those results were compared with those of a group of matched control participants.

The mean age of the women was about 28 years.

The Warwick researchers found that in vitro invasion was significantly attenuated by sera from women with PCOS after 6 months of metformin treatment (P < .01). Moreover, cancer cells appeared to spread about 25% slower in those sera.

On the basis of their evaluations of the sera with various assays, the researchers said, "These effects appear to be associated with NF-κB, MMP-2/9 and Akt and Erk1/2 signaling pathways that are known to be important regulators of inflammation, tumor invasion and metastasis."

The authors emphasized the findings need to be investigated further with randomized controlled trials.

Commenting on the article, Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado, Denver, said, "This is an interesting study because we've been looking for things that metformin may do that can help women with PCO. Their adverse metabolic status is something, we think, that puts them at risk for the development of endometrial cancer — it's not just their reproductive hormones. So it would be kind of cool if it turns out this drug can actually improve outcomes."

When asked whether metformin might also eventually prove useful in the prevention of endometrial cancer, she replied: "That's an intriguing idea," but added, "On the basis of this in vitro study, using a single endometrial carcinoma cell line, I would not leap to giving metformin to all PCO patients who have a hyperplasia or a cancer."

"But," she noted, "I certainly want to learn more about this, because it might make a difference."

The study was supported by the General Charities of the City of Coventry. The authors and Dr. Santoro have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. 2011;96:808-816. Abstract

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