My areas of expertise or of interest are within hormone receptor positive disease and trying to discriminate the different groups that there are from a prognostic point of view and from a predictive point of view. Also within HER2 positive we’re trying to identify novel biomarkers that can help us make better treatment decisions, especially regarding anti-HER2 therapies. Also within triple negative we’re doing some studies where we’re trying to dissect this group of tumours into different groups and try to find additional biomarkers beyond the ones we have which are basically none.
What biomarkers are you looking at?
On the one hand within HER2 positive disease, for example, we have identified at least four different subtypes within this group – luminal A, luminal B, the basal-like and the HER2 enriched. We’ve shown in the past that within HER2 positive disease if you are HER2 enriched by gene expression you respond more to anti-HER2 therapy in combination with endocrine therapy, for example, or without but even without chemotherapy. We’re further trying to pursue this as a potential biomarker that will help identify a group of patients with HER2 positive disease that in the future they could be cured with just biological therapies without the need of chemotherapy. I think this could be definitely very relevant.
Within the hormone receptor positive group we are trying to dissect that group into, again, the different subtypes and try to see if one of them responds more or less to novel agents like CDK4/6 inhibition. We have already data out there suggesting that within this group, the hormone receptor positive, if you are non-luminal by gene expression probably you don’t benefit from these drugs. So novel strategies are needed and we’re trying to find which ones in the lab.
Within triple negative we are mostly focussing on a group of tumours that is a minority but is a group of tumours that are probably driven by androgen receptor among other alterations and it is our focus to try to find new targets within that group and new drugs that could help improve outcomes in a group of patients that today we only have chemotherapy.
How do you see treatment for breast cancer changing over the next 10 years?
Definitely a lot it’s changing. The complexity is high but CDK4/6 inhibitions are here to stay, not only in hormone receptor positive disease but also in the other groups. The big question is going to be how are we going to combine these treatments, how are we going to do the sequential treatment upon progression, that’s where I think the challenge is. How are we going to study these tumours as they evolve? Certainly we have technologies like ways of measuring in the blood the DNA and mutations and tumour burden but probably that’s not enough compared to lung cancer where we have known particular DNA alterations that are oncogenes in breast cancer. Probably we need to go to the tumour and study more RNA, protein, the epigenetics. So that’s a big challenge. Definitely what I envision is that we need studies that upon progression CDK4/6 inhibition, for example, we can study that tumour and start dividing the different groups and running trials in these different settings.
I do envision a setting where things are changing. From a DNA perspective I do believe oestrogen receptor mutations are also probably going to make an impact in the clinic as well as HER2 mutations. Another question is once we have these drugs how are we going to do these combinations depending on the biology of the tumour. Should we start with one, with the other one, so the sequential is going to be critical. So a complex scenario but at the same time an exciting scenario.
What would be your take home message?
One of the main take home messages is that if we want to continue evolving and improving the outcomes of our patients with either early breast cancer or metastatic disease it’s critical that we do a lot of translational studies. Of course these are not always readily available but unless we do that it’s going to be very difficult to really move the field forward. So participating in clinical trials, in translational projects today and now especially that we’re identifying subgroups of patients that are now a minority, either we do these in collaboration not only in Europe but across the Atlantic or we won’t be able to answer important clinical questions. So that’s my main take home message.
