You’re presenting here a study about something which is affecting resistance to endocrine therapy. Can you tell me what it is you were trying to look at when you configured this study?

Yes, we know that 60-70% of patients with breast cancer express an amplification of a gene. This gene is fibroblast growth factor receptor 1. We saw that patients that expressed this kind of gene are resistant to endocrine therapy. We don’t why, exactly why, and we are looking to find an explanation.

And you’ve got a preclinical study initially. What did you do in the study?

We found in patients treated with anastrozole endocrine therapy an increase of nuclear FGFR1 expression. We know the nuclear FGFR1 from 1984, it’s a long time, but never has it been associated with endocrine resistance. We saw an increase after the treatment with endocrine therapy and we try to understand why there is this increase.

Can you explain a little bit more about what this nuclear FGFR1 is?

Yes, nuclear FGFR1 is the receptor, the FGFR1, can be found on the membrane, in the cytosol but, interestingly, it’s possible to find this receptor in the nucleus too. This is strange – why is this receptor in the nucleus? In some papers, recent papers, they showed that this receptor combines DNA that describes is implicated in the resistance to the cancer. Now we have found that this receptor combines with the oestrogen receptor too and drives this resistance.

So did you suspect that it might be associated with a resistance to endocrine therapy?

Yes, we suspected this function of nuclear FGFR1 is really important to drive endocrine resistance.

And what, in fact, did you find in the study?

We found that treatment with anastrozole, with endocrine therapy, increased the nuclear expression of the receptor and increased the bonding with the oestrogen receptor, increased the interaction between the two receptors. This interaction could drive the expression of that are related with resistance, with cancer resistance.

This is in preclinical studies, what do you think would happen in a clinical situation?

Really we found this interaction in the tumour samples too in patients treated with anastrozole and we found the same in the cell line. We started with the patients and we go to the bench.

What then, do you think, could be the clinical message coming out of this for cancer doctors?

I think the most important clinical message is the patients with oestrogen positive, receptor positive, and with FGFR1 amplification should be treated with an FGFR inhibitor plus endocrine therapy.

And are there FGFR inhibitors available to do the job? Can you consider targeting this molecule?

Yes, there are two studies ongoing that use an FGFR1 inhibitor, one without endocrine therapy and one in combination with endocrine therapy, in the USA and Europe.

But you’ve established it definitely has a role so what would you summarise as the bottom line message for doctors coming out of all of this?

Check the amplification of FGFR1 before starting the treatment with endocrine therapy and if there is amplification we have to consider putting these patients in a clinical study.