STORM trial to identify genetic variability in metastatic breast cancer

Bookmark and Share
Published: 9 Sep 2017
Views: 2331
Rating:
Save
Dr David Cox - Cancer Research Center of Lyon, Lyon, France

Dr Cox talks with ecancer at the ESMO 2017 Congress in Madrid about the STORM trial, a clinical cohort study to identify genetic variability related to metastatic phenotypes. 

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

STORM is SNPs to risk of metastasis which is a clinical trial that we started looking at basically clinical characteristics and germline genetics of 1,500 metastatic breast cancer patients.

Obviously there are some genes that are going to be very widely known but you’re looking beyond those genes or finding different types?

Actually we don’t really know what genes we would expect to find which is why we took the option of using a genome-wide association study which is basically looking at a few hundred thousand variants across the entire genome to see if we could find anything.

I was thinking more along the lines of breast cancer predisposition genes generally, like BRCA, being in the public sphere as it is. So were there any that leapt out at you from this genome sequencing?

Not yet. We’ve used a genotyping approach, it’s not actually sequencing yet. So we’re looking at specific points that we know are variable between different people and looking at the association between those points and the outcomes that we could have in the trial. It’s actually quite interesting that you talk about BRCA1 and BRCA2 because there’s actually very little evidence to show that even women who carry these mutations, while their risk is much higher, it doesn’t necessarily translate to a quicker progression or higher mortality.

Is this then just filtering down through the results, trying to eventually approach those genes?

Exactly. So the idea is to really try to find very common low penetrants so very minor alleles that would be very interesting from a clinical point of view afterwards. We’re at the point now with clinical trials that we were with breast cancer risk in the early 2000s where this is really one of the first studies that is looking at germline variation and how it’s going to associate with outcome. Ten years ago we were at the same spot with breast cancer risk factors so now we’re to the point where there are a few hundred polymorphisms, these very common variants that are associated with breast cancer risk, and there are trials that are starting to look into using those variants to stratify screening. What we’re hoping is that in the next couple of years as we gain more information we’ll be able to use these variants that we’re identifying now as stratification variables in future clinical trials.

You mention this is just at the genotyping stage now, what’s the plan for progression, next steps?

The next steps is to keep turning the crank and looking at all these variants that we’ve found that are associated with outcomes. Also to build up a consortium of international studies that are very similar so that we can replicate and have more statistical power to find more variants.

Any plans to go beyond the genome, looking at all the other omics that are available?

It’s difficult to try to roll everything into one. Building these cohorts is expensive and takes a lot of time so we took the option of only collecting blood samples at the time of inclusion and we don’t have access to tumour samples or anything like that. So it’s not always easy to go into a full omic approach.

Not to pin a date to it or anything now but when can we start to maybe expect to see first results, maybe interim results, coming from the STORM series?

The first results are coming out this week so that’s really the reason why we wanted to put in a late breaking abstract here at ESMO. We do have some interesting results and actually STORM was designed to work with another clinical trial called SIGNAL which is early phase breast cancers. So that’s 10,000 breast cancer cases that have not necessarily progressed yet. So we’re able to compare the two and that’s what we’ll be presenting here.

A conference like ESMO is the perfect chance to bring together different international collaborators, different aspects. Has there been any interesting feedback from people who have seen your results and thought, ‘I know just the thing for this’?

Not yet because we’re presenting them tomorrow morning but I’m sure that once we do present them there will be a lot of people knocking on our door to try to gain more collaborations.