AACR 2012 Annual Meeting, March 31st - April 4th, Chicago

Metformin’s effect on breast cancer

Dr Vuk Stambolic – Ontario Cancer Institute, Toronto, Canada

The results from diabetics on metformin use have been actually really, really interesting and suggests that diabetics taking metformin actually have cancers that are not as aggressive and not as frequent and, of course, not as deadly. So that prompted a lot of interest in the last few years, in many different types of cancer, to explore the possibility that metformin may be an anti-cancer agent. Several potential mechanisms of action of metformin have been proposed and those are currently being explored, both in the pre-clinical and the clinical setting and are showing some very exciting results.

How does the drug achieve its effects?

What we’re finding interesting is that in order to achieve direct effects of metformin that would potentially inhibit signalling via the mTOR signalling pathway, similar to some of the other drugs in the rapamycin class, we need levels of metformin that are very, very high and they’re really not achievable in giving to patients; so we’ve been exploring quite a bit a potential for an indirect mechanism of metformin action. We’re conducting a small clinical trial, it’s a window of opportunity trial, phase I/II trial, where we’re giving metformin to women with new breast cancer in between their biopsy and their surgery and collecting both the metabolic primaries as well as tissue material from those two time points and, in fact, comparing this in a fairly comprehensive manner, trying to understand what are the possible changes the metformin may be inducing in these individuals.

Are there any preliminary results?

We have preliminary results that are most consistent with a limited action of this drug via possibly an indirect mechanism. When I say indirect mechanism, that is the mechanism associated with the insulin lowering property of metformin, similar to the effect that is actually seen in diabetics taking this drug. So by regulating gluconeogenesis in the liver, metformin very potently can reduce circulating insulin levels and our results are consistent with the possibility that that reduction in insulin may actually reduce insulin signalling in cancer cells and in doing so induce an anti-proliferative and potentially even a prehepatic response.

Does the cost and availability of the drug affect the study?

Very much so, and this is both good and bad. It’s easy to get to this drug but at the same time placebo costs an awful lot. We actually don’t have… all the funding for this endeavour is actually public and we have secured certain help from pharmaceutical companies building the placebo for us but it is an interesting and very exciting opportunity, also because it may impact cancer and cancer treatment in less developed countries that cannot afford some of these personalised treatments that are coming along. We’re also conducting a fairly large phase III clinical trial in almost 4,000 women with breast cancer who will be on metformin after their treatment for five years and we will ask this question of whether metformin can in fact impact recurrence in these patients. This is a much larger endeavour and it is a combined action of both US and Canadian clinical trial agencies. Again, interestingly, all the funding for this comes from public sources.