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So we are here today with Professor Michael Gnant and we're really excited to talk about, ask you and the advances in breast cancer that were presented at Asco 2023. Professor. Gonna could you perhaps give us a little understanding of your research interests and perhaps a little bit about, about your career so far and then we're going to dive straight in to ask you. Yeah, thanks for having me fill uh I'm a professor of surgery surgeon by training uh with a particular interest in surgical oncology and recently narrowing down on breast cancer. Uh I'm also coordinating the Austrian breast and colorectal cancer study group that has been able from our small country. But because we have uh so wonderfully great patient's who in in large numbers contribute to our prospective trial more than 30,000 so far in the last three decades. And that gives our tiny country the opportunity to contribute a little bit more than we are in terms of geographical size to the knowledge uh with, with the focus on uh endocrine treatment in early breast cancer, which which is also um uh one of my main research interests, but we we also are doing a lot of research in in neo adjuvant trials um as well as some specific issues such as problem a Bishan bone targeted treatment uh and so on. Super, thank you so much. And if someone wasn't able to make it to ask, oh, this year, what, what was everyone talking about with regards to advances in the management of, of breast cancer? What were the kind of key takeaways, the key papers that that you think we should know about from, from your perspective. Well, esco 23 in terms of breast cancer was uh pretty much focusing on the Natalie trial um to give you some background. Uh there's a relatively new class of drugs so called CDK 46 inhibitors cell cycle inhibitors that in recent years have become standard of care in hormone receptor positive metastatic breast cancer. Actually, first line care, first line standard of care. And uh there is in fact a total of four of them. Uh one tell possibly is the Chinese compact that that may not arrive in the European or us markets. Uh The other one's Palbociclib ribociclib in Abemaciclib have been tested in various large clinical trials in metastatic breast cancer. First line, second line. Um having said this as always, we're trying to transfer advantages and benefits with defining the metastatic setting to the early to the curative breast cancer setting. And there have been interesting uh but also controversial results because two large uh Palbociclib based trials, the Palace trial and the Penelope be trial have been negative. So uh Palbociclib up in the early breast cancer setting so far did not demonstrate benefit been added to standard endocrine treatment. Um and quite differently. Uh Abemaciclib has uh in the monarchy trial now at the medium follow up of where years showing a consistent benefit. Uh In fact, that amounts to an absolute uh 6% benefit approximately And this is for survival uh data we're missing for the third for ribose I clip and uh suspense was increased because as uh obliged by the stock market and change the rules. There was a press least a couple of months ago that the Natalie trial which is testing the addition of ribose cycling between the current treatment in the early breast cancer setting would be positive, but with no details. And that was actually the first and probably most discussed presentation uh in the field of breast cancer uh to make a long show restored. Natalie is uh demonstrated benefit overall uh at the very early stage. So this is still an interim analysis with four out of five patient's still being on trial treatment. So one cannot call this robust at this time. But uh interestingly, even so early in, in, in the trial, um there's a clear benefit basically among all subgroups that include a little bit more of the risk spectrum that the monarchy trial had included. So it's not only highest risk patient's but also moving CDK for six inhibitors into the uh let's say intermediate risk group. Now that early there is. So that's exciting. It's good news for patient's and it could, if confirmed, it could uh let's say extend the target population of uh that additional treatment from the highest risk uh subgroup of patient's to maybe a total of 35% of all patient's with hormone receptor positive breast cancer. However, because that was the presentation of an interim analysis, uh everything correct in terms of the statistical conditions, but uh the number of events, particularly in those lower risk intermediate subgroups is still limited. So many of the discussion's uh and I I would agree with them, advise uh caution because these results need to be confirmed by uh updates with more follow up more events coming in. Uh Convinced Natalie will update their results more or less at every major meeting in the field of breast cancer. Now, in the next couple of years, uh also we have to say with, with a relative improvement of disease for survival by about 25%. That obviously makes a difference in terms of the absolute benefit wherever you are in your risk situation. So um such a 25% improvement sounds a lot. But because of the excellent overall results, we meanwhile achieving the treatment of early breast cancer, um this might be 4 to 5% in, in patient's at very high risk, but it might only be only 2%. For example, in note negative patient's and that's a three year treatment duration with the nutrition of treatment. And so discussion's will obviously be how much of an absolute benefit to we as scientific community. But also the regulators. And more importantly, eventually, the pay us uh request for what can also be interpreted as a small benefit because obviously, when you have to present of absolute benefit, you treat 98% of patient's without them benefiting. And this these trucks are not particularly cheap. Uh So uh not only in countries with limited resources, but also I would say in average countries in the western world, there will be some discussions about approval reimbursement. Uh and who really should, should, should get the additional uh treatment. It's super interesting and, and uh really interesting to kind of see the pace at which we're moving in this space where if we were looking at asking 2020 for, what do you expect us to begin to see coming out in terms of results? And what do you think are the the biggest or hottest ongoing trials and breast cancer right now? Well, you know, I think one of the interesting things is that um for almost two decades, there was not too much innovation in endocrine therapy and in fact, was uh hormone receptor positive breast cancer being the most uh prevalent subtype. Actually, the largest number of breast cancer patients around the world is affected by uh potential advances in hormonal treatment. Now, we really see an explosion of innovation. So after two decades of more or less using and optimizing all the drugs we had, we are now seeing the CDK 46 inhibitors coming there, we see a complete new generation of oral surgeons that are moving into uh large clinical trials even in the admin setting. Uh and even beyond that, I mean, there were some interesting posters on on new top type of trucks. They're gonna so so called pro tax or syringes, complete estrogen receptor. Uh the graders that will have to be tested. So there's really a lot going on. It's difficult to predict what might be available in 24. But there is one overarching theme I I think and, and that's our current standard of care is aromatase inhibitors. These drugs are generic. So I wouldn't exactly call them penny drugs. But I mean, this is about the monthly treatment cost of 10 to 20 lbs euros, uh bucks uh more or less and substituting them with drugs that at the moment have monthly caused of 34 5000. Um uh is a huge challenge particularly because such a large number of uh individuals uh is potentially affected by that. So that's going to be a huge discussion. The the question is, can we somehow better define on an individual basis using biomarkers using predictive factors who really has uh sizable benefit because it might not be very likely that we will be able to afford uh these treatments for everybody, not even starting to talk about countries with limited resources. Uh And one interesting technology that I think will um I'm very optimistic that will pre wail other than some other attempts in the past. For example, when we were trying to hunt down circulating tumor cells, that technology never really, there were some interesting reports but it's so difficult to define it. But there is now a technology that is increasingly used also in the context of clinical trials. And that's the measurement of circulating tumor DN A. Um And that's both interesting in the high risk segment. So let's see in patient with large tumors neo adjuvant treatment to see because we can actually find circulating DNA stemming from, from tumor cells in the majority of these high risk patients'. And we can monitor um how our treatments are providing clearance of the circulating tumor D in. And that has been already shown to be predictive factor also for long term outcome. On the other hand, in, in uh particularly Luminal breast cancer, we are still with all the advances and excellent prognosis. Overall, we see the issue of later currencies. So, um whatever might have been written in old books after five years, you know, you know, if, if you remain healthy until then, then you're fine, that's simply not true for hormone receptor positive breast cancer. So, while these patient's overall have an excellent cure rate of 85 90% but there is a constant uh prevalence of late recurrences, maybe half a percent per year. But in 20% 20 years, that also amounts to 10% of all patient's. So, um it's a little, still a little bit of mystery how that works. Uh in terms of the cancer biology behind, I think the most common understanding is that micro metastases can go to a dormant state and eventually wake up and cause we're clinical recurrence and identifying this early. And the technology I was talking about circulating tumor d in a apparently is able to identify a patient that will have clinically work recurrent disease with a lead time of about even uh 12 months or so, which in theory gives enough time to intervene. Now having said this, we still, I don't know, but these trials are starting now or have been started now around the world, whether we can intervene a situation because the diagnostic alone, I mean, if you have a patient in the same, yes, MS Miller, we found circulating to Medina in your blood. And then Miss Miller will ask, so what are we going to do about this? Um Unless we can demonstrate that we can successfully intervene in such a situation, it's still a theoretical researching, but it's not unlikely that uh we might be able to define interventions at this point. More or less keeping the disease at bay, keeping these cells uh sleeping, so to speak, uh providing clinical uh disease free nus so, so that's probably um uh the the hottest topic, so to speak. And I would expect that in, in the next couple of years, we're going to see very interesting results around this subject. Absolutely fascinating. So, we're talking about early treatment, keeping the disease at bay. And um uh and actually thinking about the earliest possible intervention for, for, for patient's when we, when we find that they're at risk. Really interesting. Thank you so much for your time professor gone. And we really appreciate that, that summary of the hottest topics in breast cancer from Moscow 2023 and a little glimpse of what's going to come in the next couple of years. Thank you so much.