BACR & ECMC: Therapeutic interventions for cancer prevention

Chemoprevention of breast cancer recurrence

Prof Rob Coleman – The University of Sheffield, Sheffield, UK

I’m talking about the possible use of bone targeted agents in the prevention setting. We’ve used bone agents for decades, either to treat osteoporosis or to treat advanced cancer but over recent years people have tried to look at their role in preventing breast cancer recurrence which they are able to do that. So the next question is could they also have a role in the prevention strategy.

Can you tell us more about the mechanism?

There are two main classes of bone targeted agents – bisphosphonates and RANK ligand inhibitors. The potential mechanism for bisphosphonates affecting the development of breast cancer is much more tenuous and, in fact, in my presentation I will probably conclude that the data suggests that that’s not a particularly exciting strategy. We have data from a very large meta-analysis which showed that bisphosphonates stop breast cancer recurrence and stop breast cancer deaths but had little or no effect on contralateral breast cancer.

On the other hand, denosumab is an inhibitor of RANK ligand and RANK ligand RANK signalling and that pathway is important in breast development. It’s important in breast development and the effects that progesterone has on the breast and it seems to be particularly relevant to the development of breast cancers in BRCA1 gene carriers. There was a very nice publication in Nature Medicine just within the last couple of weeks showing this is a really quite exciting potential therapeutic strategy.

Can you tell us more about the early breast cancer clinical trials group?

The early breast cancer clinical trials group was a meta-analysis which I co-ordinated with the Oxford group looking primarily at women who have already got breast cancer and do these drugs prevent recurrence and do they prevent breast cancer deaths. In post-menopausal women they clearly do that, they reduce about one third of recurrences in the bone where they’re acting and about one sixth of breast cancer deaths. So this is an important development, it’s another of these repurposed treatments for breast cancer for which we don’t have a specific licence and all the issues that that raises. But certainly in this country adjuvant bisphosphonates are becoming part of standard management.

Can you tell us about the IBIS3 study?

IBIS3 is a study looking at women who are about five years out from their original breast cancer diagnosis, looking to see whether things like bisphosphonates or metformin or continuous endocrine treatment can both prevent late recurrence of their breast cancer but also do they have an effect on new breast primaries.

What are your thoughts on the BACR conference?

Yes, it’s an interesting meeting for me. It’s not my normal area, I’m a medical oncologist, I’m usually involved more in treating existing cancer patients; I am part of the IBIS programme. So for me this is quite nice, taking me out of my comfort zone. I’ve heard some interesting science and some interesting new concepts so it’s been very educational for me and I’ve enjoyed it.

What roles do you see prevention taking in the future?

I think each breast unit needs to define its own strategy. That might be run by breast physicians and breast oncologists or it may be run by breast surgeons with an interest in family history and prevention strategies. There are many ways of doing it, it’s just important that there is a dedicated clinic set up and a research programme that patients within each locality can plug into. So Manchester would be a great example of where that happens, that’s something to emulate in our own units.

Any final thoughts?

So thinking a bit more about the prevention setting, these recent pre-clinical data showing the importance of the RANK ligand RANK signalling pathway in breast cancer does open this opportunity to use denosumab, which is an antibody, and this would be given on an occasional basis, probably every six months by subcutaneous injection. It’s extremely well tolerated and extremely safe and trials are being developed which we hope will start within the next twelve months probably targeting specifically BRCA gene carriers in the first instance although there may be a rationale in a broader range of breast cancers. So this approach is really exciting, it’s a knight’s move away from the bone effects of these drugs but potentially a very exciting new development.