I think that this is quite a neglected focus at the moment because most of the efforts have been focused on curing the tumours. Of course we had very good results in the past because, just to let you know, the most frequent histotype of breast cancer, that is breast cancer with the expression of oestrogen receptors, has a chance of cure reaching 80%. But still we have 20% of the patients which eventually will relapse. We know that we can do all our efforts in order to try to cure these patients, or at least try to chronicise their disease just in order to improve the survival.
This is a very fascinating issue in my opinion, because we are at a congress dealing with the cancer patients’ empowerment, and the patients in this field can really play a pivotal role. Because, of course, this is just a matter of putting together technology and, I would say, the psychology of the patients and also ethical issues, because we have to try to apply the most recent findings of technology and research just in order to find out how the tumour of these patients has changed over its natural history. Because we know that the survival of these patients may be reaching more than ten, fifteen years.
We usually have data based on the primary tumour. Then there is the relapse, but meanwhile, we know now that something happens and we know now that this tumour may be modified according to evolutionary laws, as it happens in ecology, for example. The tumour is modified according to the treatments and may develop resistance to a specific treatment. So, for example, for ER positive patients, we used to cure these patients by using aromatase inhibitors or tamoxifen, and we know now that these tumours may develop a specific resistance to these treatments. So it is very important to find out which kind of resistance these tumours may develop just in order to know how to treat them and how to cure or chronicise the disease.
We know from the literature that there is a specific mutation in one gene, that is the oestrogen receptor gene, that occurs in approximately 20% of these patients. Our group, we had a very interesting study last year. The study was published in January 2017 in Nature Genetics and we found an alternative way by which these tumours may escape the treatment. They can do that by amplifying a different gene, the aromatase gene, and so by amplifying the copies of the genes they may resist the specific treatment of aromatase inhibitors. These are quite new data and we are going now to develop the diagnostic test and thus to prove in a larger series the prevalence of this disease and how to cope with this specific resistance.
These tumours remain ER-positive, but are they expressing another type of receptor for ER?
They are expressing ER positivity and we used to evaluate ER by immunohistochemistry, by a clone that is FDA approved, so we are quite sure that they are expressing ER. But then they still are expressing ER, but they may have an activating mutation on the ER gene or an amplification of the aromatase. These are the only two mechanisms by which these tumours may acquire resistance to the treatment. That is very important in my opinion, because this tumour represents 75% of all the breast cancer and this tumour is usually treated for five or ten years so they have time to develop the resistance. We should find a way of evaluating quite earlier, as early as possible, when this kind of resistance may happen.
This is very important because we have to get trust with our patients because we should find a way of applying… I would define it as a molecular follow up. Of course when the disease relapses this may be too late because, of course, then there is a clinically evident disease and so it is very difficult to cure the patient. But what happens if we could demonstrate the acquisition of a specific resistance by using, for example, a blood sample?
We can do that now, we can do that for the ESR mutation, as is being reported and already applied in clinical trials, but our group, which includes, let me quote them: Luca Magnan in London, and Saverio Minucci working at IFOM, we are willing to transfer our test that we applied on the tissue taken by the relapses in a retrospective series, we are willing to transfer this method on plasma. So, we could evaluate the alteration in the plasma, the DNA of our patients. So we have to talk with our patients to involve them. They should be willing to, I would not say just to participate, but to drive our studies, because of course they should be evaluated each six months or yearly just in order to try to detect the alteration quite as early as possible.
Do you think all cases will eventually relapse?
No, absolutely not. We know that we are able to cure approximately 80% of these patients, but still there are 20%. It’s quite a huge population of people that could develop a resistance at the end of the story and I think that it will be very important to let the patient know that, of course, they could have a very late relapse, five years, ten years. In fact, all the scientific community is focusing on this problem now and we are developing new drugs, new treatments and new diagnostic tests just in order to focus on which population should be treated with specific treatments.
Of course the armamentarium of our drugs is widening now and we could try to shift the specific treatment now we have inhibitors of CDK4 and 6 in the clinic. So we could try to evaluate which kind of treatment may improve the survival of patients being driven by specific molecular alterations, this is our goal now.
