Nancy Lin, MD; Sara Tolaney, MD, MPH; and patient advocate Lianne Kraemer discuss new developments and promising areas of research in metastatic breast cancer at Dana-Farber and beyond.
Good morning. My name is Dr nancy lim and a medical oncologist at Dana Farber Cancer Institute in boston massachusetts. I'm joined today by my colleague Dr Sarah Delaney and by patient advocate MS Leann Kramer for our 11th annual metastatic breast cancer forum series. Um as we are as we did last year, this will be a virtual forum series. Today is the opening event and then we will have additional um webinars to come in the months to come. And so watch out for those announcements again. Today is the welcome session. Um This will be led by both myself and Dr Sarah Delaney and dr sorry and Miss Leann Kramer will be moderating the Q and A to follow next slide. I want to make a special acknowledgement to my series virtual forum series. Co chairs melissa Hughes on the left and Lauren buckley on the right without them both. This virtual forum program, but really the entirety of our embraced metastatic breast cancer program would not be possible. And I just want to thank them for their many years of contributions to this program. And finally, I want to give special thanks to Elizabeth frank who is a patient advocate who has worked with us for more than a decade on the embrace program. Um she has retired but has still agreed to help help us and to guide us and we're really incredibly grateful for everything that she's done over very many years. Next slide. And finally I wanna thank members of the embrace patient advisory council. Members of the council have provided their time and input and feedback into the programming of this forum as well as well as other educational patient facing programs that we offer. And so appreciative of all the time that people have taken out of their days to be able to um to be able to provide so much useful feedback. That's why. So today's session format will include a keynote address from Dr Sarah Delany and then I'll be speaking about recent advances in metastatic breast cancer and a brief update of the embraced program. After this, we've tried to leave plenty of time for question and answer and this will be moderated by MS Leann Kramer. MS Kramer is a patient advocate. She initially trained as a pediatric speech pathologist. Um but since her diagnosis of breast cancer stage two initially and then metastatic breast cancer, she's really become an patient advocate um and has been involved in many organizations including the NBC Alliance, met a fever and others um and has provided a significant guidance as well in our brain metastases program here at Dana Farber. So without further ado, I'm gonna pass the microphone over to MS Kramer. Um and we'll go from there. Thank you Dr lin. Um I just want to remind everybody that after this morning session there will be um breakout sessions later this afternoon with subtype specific discussions. Um So that's 11 30 12 30 Eastern time. So don't forget to come back for those and I have the honor of introducing Dr Delaney um who will present first Dr Delaney is chief of the division of breast oncology and Associate director of the Susan F. Smith Center for Women's Cancers at Dana Farber Cancer Institute. She is an associate professor of medicine at Harvard Medical School. Dr Delaney is internationally recognized for her research and leadership and breast cancer. Her focus is on the development of novel therapies in the treatment of breast cancer and is developing more effective and less toxic treatment for approaches for patients with both early stage and metastatic breast cancer. She has played a significant role in the development of the C. D. K. 46 inhibitors, antibody drug conjugate and immunotherapy and breast cancer. So I will turn it over to Dr Delaney, thank you so much Leanne and thank you Melissa lee ANn and nancy for for having me today. You know it's really such an honor to be able to participate in this forum and really to to open things up. I wanted to give a vision of the Dana Farber breast cancer program. I took over as chief of the program just over the last several months and you know in this role it's made me think a lot about where we need to go as a field and in terms of improving outcomes and breast cancer. So I wanted to share some of the efforts that we are doing and really also wanted to thank so many of you who have really invested in helping us improve outcomes. So thank you in advance for all that you also have done. Um So next slide please. I think as the Dana Farber breast cancer program, our mission is really to be able to have a transformational impact on the lives of patients living with breast cancer. With the goal being that we want to provide the highest level of expert and compassionate care to all of our patients. But at the same time we want to be able to learn from each and every patient that walks through our doors so that we continue to be able to improve outcomes for the next patient. Um so that is you know, I think goal that goes hand in hand is making sure again that we are taking care of patients at the to the best of our ability and continuously trying to do better and better for everyone next slide. So how are we going to actually do this? And how are we going to continue to really have such impact on patient outcomes next slide. So I think as you all know, breast cancer is complicated. Um it isn't just one cancer, it is far more complex than that. I think generally we've tried to group breast cancers into three general categories patients can have hormone receptor positive breast cancer, meaning that they can have a cancer that's driven by having the estrogen receptor present. They can also have her two positive breast cancer where in this particular case the cancers have lots of her two protein on the cancer cell that's kind of sending this continuous growth factor signal into the cancer cell which has really become a clever way for us to be able to to target and treat those cancers. And then there's also what we call triple negative breast cancer, which to date has really been defined in a way by what it's not. Um so not having the estrogen receptor, not having the progesterone receptor and not having the her two receptor. But we've actually learned that it's far more complicated than defining it by what it's not. And in fact there are lots of things that it is that have helped make tremendous impact on patient outcomes by us being able to have so many new treatments available by understanding the biology better at next slide. So again, these are the general buckets we had thought about categorizing breast cancer as again, hormone receptor positive, triple negative and her two positive most common type generally is hormone receptor positive, which is about two thirds of all breast cancers and triple negative and her two each are around 15-20% of each of all the breast cancer cases. And next slide. But I think as I was alluding to these buckets are probably not fair because we learned that not everyone who has a hormone receptor positive breast cancer has a cancer that behaves the same way. Just like not all her two positive cancers have cancers that behave similarly and same with triple negative breast cancers. And so as we dig down into the biology of these cancers, we realize that you can separate them into multiple more ways. Um So you can see this bucket at the top where hormone receptor positive breast cancers can and separate into different subtypes, what we call Luminal A, Luminal B. Really suggesting that the biology of all these cancers isn't all the same. So the buckets aren't technically all correct that you can get far more complicated in trying to tease out people's individual cancers and next slide and I think this is pretty exemplary of how complicated cancer has become. So if you look at triple negative breast cancer again, we sort of in a silly way had defined it by what it's not, we're saying again, it doesn't have estrogen receptor progesterone and her too. But in fact it does have a lot of different things as you can see here. So it turns out that about 40% of triple negative breast cancers have this receptor on it called Pd L. One, which in fact is a cancer's way of trying to evade the immune system. You know, the cancers and truth shouldn't develop. They should in your immune system should have found that cancer and killed it. But cancer cells in their own way want to figure out a way to outsmart our bodies. And so some of them will turn on this pD L. One receptor to in essence hide from the immune system. But now we've learned we can be clever and fight back and actually turn off that blocking signal with the use of immunotherapy and allow our own body's immune system to kill the cancer cells. So understanding if that receptors present is actually really important is someone who has triple negative breast cancer. It's also really important to understand if someone has a um genetic mutation, specifically what we call a germline bracket mutation where we have found that these oral drugs called part inhibitors works very well in patients with this particular mutation. And so again really important to know if if this is present. And then you can see a whole his list of other protein markers that can be on cancer cells that were actually learning a lot about because it is allowing us to target cancer cells. So one example of this is, it turns out that pretty much every triple negative breast cancer cell has this protein on it called trope too Well that's allowed us to develop fancy drugs that can target that receptor and deliver chemotherapy into that cell. It also turns out that triple negative breast cancers, even though they're her two negative turn out to have some of them have a little bit of the her two protein on it and we can again use it as a target. So it's really important for us to understand the biology too much more in depth way than just these simple buckets and that's what we're really doing now too. And I think because of that have been able to develop so many new therapies that are really so effective for so many patients and really moving towards personalizing care for our patients by understanding their individual tumor next line. So I think one of the goals of our particular breast oncology program is to be able to learn about the biology of the cancer so that we can improve outcomes. And I think because it is so complicated, not just one individual can do this, I think it takes a team, people who have different expertise is in different areas. So for example, we have the smart people in the laboratory who study the biology of the cancer. We have translational scientists who are able to understand what's going on at a patient level and understand the science in that particular patient. And then we have clinicians who are taking care of patients and seeing what therapies are working and not working. And we have patients who are patient advocates who are very involved in helping us figure out how to appropriately deliver treatment to patients. And we need all of these people together in one room to take everyone's different level of expertise to be able to learn the most that we can and so what our group has done if you go to the next slide is we've actually tried to do this in a way that we can make big strides in outcomes for patients by taking everyone's expertise together. And so what we've done is formed different working groups that are focused on different areas of breast cancer, where we bring all different levels of experts into the room on a regular basis to be able to learn from everyone and their experiences so that we can move the field forward and next slide. The other thing that we've really focused on is learning again from every patient that walks through the door. There's something to learn about everyone individual cancer and their experience. And it's really important that we take away all those experiences and continually use those experiences so we can learn and do better. And so what many people in our group, including nancy's, who's actually led most of these efforts, is putting together what we call a cohort program so that each patient who does come through the door, we can collect their clinical data and be able to learn about what treatments they received, what worked, what didn't work. Um and along the course of that trajectory, also collect bio specimens next slide. So what we have been trying to do is more uniformly collect tissue, blood, even stool, uh and be able to learn as much as we can from each individual patient, so that we can figure out why it, is that a particular drug worked or why it is a particular drug didn't work So that again we can move towards personalizing care for patients. Next slide I think what we've learned though is there's so much that we can learn from each individual patient. One particular example is collecting blood for what we call circulating tumor DNA. It turns out that cancer cells can emit their D. N. A. Into the bloodstream and then we can collect this just from a simple blood draw and be able to take that blood detect that D. N. A. That the cancer cell had spit out and sequence it so that we can understand what mutations are driving that cancer to grow. And this is really critical if we're trying to make treatment decisions. So if you go to the next slide you can see that this blood can be used for so many different things and this is what we're doing research on to figure out how we can best utilize this drug that this information from these blood drugs. One idea behind this is if we could draw blood and figure out which patients cancers are responding before even getting a cat scan. For example if we could just see in the blood that the amount of the circulating tumor DNA. Is decreasing. That could be an early signal that the drugs are working and that could help us figure out again how to tailor therapy. Whereas if we see the level of the C. T. D. N. A. Rising maybe that's suggesting that the drug isn't working. And so can we use such information to try to you know modify therapy based on what we're seeing in the blood. The other thing we could do is actually learn what mutations are driving that cancer to grow and those can evolve with time. So some of patients getting a particular drug and we see that a particular mutation arises which could be why that drug could stop working. Can we then target that mutation to overcome that resistance that's being developed to that particular drug? And so I think this information can help us tremendously and so what we have been doing and many of you thank you for participating in this. Many of you have allowed us to collect your blood serially over time so that we can learn why a particular drug is working, why it's not working with the hope being that this can be something that we standard li do. And in fact there are companies that run these kinds of blood draws for us. And I think many of you have had them done as we do periodically send these kinds of tests so that we can understand what mutations are there and hopefully figure out if there are drugs that can target that mutation and next slide so I think you know because cancer is so complex we really tried to build what we call a translational hub. So a place where we can integrate all of this information that we're learning the information from each individual's patient experience with all the results from the blood, the tissue and the stool so that we can integrate all the information in one location. We've hired research scientists, pathologists um and really a whole team to be able to collect these specimens from patients and be able to learn the most that we can so that we can improve outcomes. And next slide. I think the other thing that we're doing is really trying to build a whole host of clinical trials so that patients have access to drugs at the earliest time point that they can um you know it does take time for drugs to get from testing to really becoming a standard FDA approved drug. You can see here in this sort of schematic that sometimes we figure out what drugs can work based on understanding what targets are present in a cancer cell. And then we need to test that drug. And so when we first test a drug that's never been tested in a person before, we have to do what we call a phase one trial where we need to figure out what the dose of the drug is, how it's tolerated and figure out what the optimal doses to use. And so if we see a good signal in the phase one study and we can figure out a dose that seems to be well tolerated. Then we move to what we call a phase two trial where we're trying to understand how well the drug works in a larger number of patients. And if it turns out that drug looks really promising and that a lot of patients are benefiting from that drug, then we need to move to what we call a phase three trial where we compare that new drug to the drug that is considered standard to use in that particular setting. And if the new drug seems better than the standard drug that finally leads to FDA approval. But as you can see, that's a process to go from the lab to phase one trial to phase two trial and then eventually to phase three to make it a standard available drug. And so being able to have access to these drugs before they become standard is really important because many of these drugs are so effective as we're developing them, that it's really important for us to make these available to our patients. So in fact, our breast oncology program has over 60, actively enrolling trials, the majority of which are actually for patients with metastatic breast cancer. So that we can personalize treatment to the patient, understand which particular drugs may be the best for the patient and and be able to give them access to those drugs as early as we possibly can. Next slide one of the examples I think of a really exciting new type of drug that nancy is actually going to get into in more detail is a class of drugs called antibody Drug Conjugate. And I think, you know, part of the idea behind these is this was figured out based on the biology of cancers and so understanding that biology again has had dramatic improvements. So if we can figure out that a cancer has a particular protein on its surface just to use as a target, then what can happen is that an antibody combined to that target? And if that antibody is linked to chemotherapy, what happens is that whole antibody with its chemo gets into the cancer cell and then releases all the chemotherapy into the cell and kills that cell. And so it's a really clever way to get a ton of chemotherapy into the cancer cell and spare the patient get all that chemo exposed to healthy cells. The other really clever benefit is some of these newer drugs are so smart that that chemo that went into the cancer cell can diffuse through the cancer cell and get into the neighbor of the cancer cell. And so then it could kill the neighboring cancer cell even next door to it. And so it's just a really clever way to get the chemotherapy in and allow it to kill that cell and its nearby neighbors in a very potent fashion. And nancy is going to tell you about some of these new drugs that have come out and several of them have actually now just recently been FDA approved where we are seeing dramatic outcomes and patients just simply by knowing if that target is present on the cell and being able to deliver chemo in a personalized fashion into that cell next leg. So I think as you can see, I think we've come a long way and trying to understand the biology of the cancers. And again, breast cancer isn't one disease. And understanding the biology in a more refined way I think is going to help us make tremendous improvements in outcomes for our patients. And I will say that is really the goal of our whole program and I think what we all really enjoy doing and seeing is being able to help patients and have an impact on their lives and continue to improve outcomes for for all that we see next side. And I think the summarize as well and what the goal of our program is is once you chose hope, anything is possible. And I think that is what really drives all of us to continue to make big strides and outcomes for breast cancer care. So with that I would like to turn it over to my colleague. So if you go to the next slide, I'd love to embrace, to introduce dr nancy Lynn dr lin is a force in breast oncology and she is not only the director of our embraced metastatic breast cancer program, she's also the director for our breast cancer brain metastases program and is associate chief of the breast oncology program. So she wears many different hats. Um and I just want to turn it over to her and let her tell you more about all the improvements we are making in breast cancer. So thank you so much nancy. Thanks sarah. So I wanted to spend the next few minutes talking about recent advances in metastatic breast cancer and also provide a brief update on the embraced program. Um I'll take the time right now to just remind you if you look at the bottom of your zoom screen you'll see a little icon that says Q. And A. Um and any time you can click on that icon and enter questions and we are reserving time at the end for your questions, you can enter them at any time, we will go through them. We'll try to get to as many as we can get through in the Q. And a time at the end. Alright, next slide So you've heard from DR Delaney already about breast cancer subtypes. And just as a reminder estrogen receptor positive means that the cancer is estrogen receptor and progesterone receptor positive but the her two is negative by our classical testing. Her two positive means essentially her too high positive. And so that's any estrogen receptor status but the cancer has to be positive by this hC test or by something called fish and triple negative is negative for these three markers. So estrogen progesterone and her two negative. If you're not sure what subtype of breast cancer you have. It's a really good question to ask your doctor because so much of what we do now and the treatments that are recommended are really based on the breast cancer subtype. And then a couple more comments is that we're going to talk a little bit more later on about what this her too low new category is and what that means. And finally there is a distinction between ductal and lobular breast cancer. And just to know that for most patients with lobular breast cancer the cancer is estrogen receptor positive. Although there are exceptions. Next slide. So first I want to talk through advances in estrogen receptor positive breast cancer and then I'll do each of the other two subtypes. In turn the highlights that I want to go over today are the use of and her two or T. D. X. D. For patients who have her two low tumors. Um The clinical trial results from a recent study of trade LV. And finally um a little update about a medicine called Ellis restaurant and what I'm not gonna have time to cover today are a lot of other things because we also give part inhibitors to patients who have hereditary or genetic predisposition to breast cancer. Um we can sometimes give immunotherapy for patients whose tumors have a high mutation burden on tumor testing. And there are many clinical trials of new hormonal therapies targeting patients whose cancers have become resistant to hormonal therapy. That's right. So I copied this slide from exactly one year ago at the embrace forum and I put it here because I think it's important to see how much progress we've made in just one year. So last year everything that's kind of grayed out are actually the treatments that were not yet FDA approved or available and really could only be accessed through a clinical trial. And then if you go on to the next slide you'll see where the status of these drugs are. So just to go from left to right we still start most patients with hormonal therapy and a C. D. K. 46 inhibitor. So that could be I brands or kiss galley or raise any oh patients who have worsening of their disease often go to another type of hormonal therapy usually with either ab elicit otherwise known as Peak Ray or Ever Olympus depending on the status of the patients pick three C. A mutation in their tumor. But now there's a new hormonal therapy called Alice's restaurant which I'll show you in a minute and this medicine is actually currently at the FDA for review. We still give patients chemotherapy but if the chemotherapy doesn't work or stops working now for patients who have what we call her too low breast cancer. So not her two positive and not her 20. But this sort of new in between category we are able to give a medicine called in Her two which was approved by the FDA just august of this year. And finally we are able to give patients a new medicine called Trade LV. And this was just added to our national oncology treatment guidelines in August of 2022 and is under consideration by the FDA. But we are able to prescribe it at this time. Next slide. So you've already heard a little bit about what antibody drug conjugate SAR. And to review essentially antibodies are natural products that our bodies make to fight viruses and bacteria infections but we can make them in the laboratory to target specific proteins on the surface of cancer cells. And we can link chemotherapy to these molecules so that we're able to deliver high concentrations of chemo into the tumor. Next slide an example of one of these so called ADCS is uh in her two or T. D. X. D. And this compound targets her two. And the chemotherapy that's attached is called direct. You can in this clinical trial which is called Destiny Rest 04 patients who had had er positive. Her two low breast cancer who had had some chemotherapy already for their breast cancer were randomly assigned to either getting her to or chemotherapy. So important to note that everyone in this trial did receive standard treatment received treatment of some kind, there was no group that just received placebo. Next slide. And what you see here are what we call waterfall plots and the way that you read them is every bar is one patient. If you see lines go above the middle, that means the patient's cancer got worse or grew. If you see lines go down, that means the tumor shrunk and each bar represents one patient enrolled in the study. The left shows the bars for patients enrolled on the in her to group. And you can see very few people had worsening of cancer as their best response. And the vast majority of people had some degree of tumor shrinkage. Whereas for patients who received traditional chemotherapy we see a larger split more people with worsening of disease, fewer people with shrinkage of disease. And the important finding from this study is not only was the tumor shrinkage rate higher with T. D. X. D. But the length of tumor control and survival were also longer with the T. D. X. D. Or in her to treatment. So this has really become standard of care. Next slide another study that came out this year was the tropics. So to study and in fact we just saw an update of this study earlier this month at the asthma meeting in paris. Um in this study, patients who had had 224 previous chemotherapies for their breast cancer received either trade LV. Otherwise known as Sarasota's a mob or chemotherapy. And just as a reminder, Triadelphia LV is a medicine that targets the trope to protein And the payload that's attached to it is the SM 38 chemotherapy. Next slide. And what was seen in this study was again, better duration or length of tumor control, Higher rate of tumor shrinkage compared to conventional chemotherapy. And then we just saw earlier this month the first um indications that being on this medicine lengthened the duration of survival. Next line. And finally what about these newer hormonal treatments. And so here I have a summary of the so called Alice Estrin data which was studied in the phase three emerald trial. Um What Alyssa restaurant is is it's very similar to fall this tree interface index which you may have heard of or had before. These are inject that's an injectable hormone. But Alyssa restaurant is actually an oral pill. It works similarly to full restaurant. And in this study compared to regular hormonal therapy which could have been full restaurant or one of the aromatase inhibitors, there was a higher rate of cancer control and this was true both in patients overall and also in the group of patients who had mutated their estrogen receptor. Again this drug has currently been submitted to the FDA for review next slide. So for er positive her two negative breast cancer, there are more options than ever before. That also means that there's more testing than we need than we did before. So we try to approach most patients for germline testing for hereditary breast cancer genes to see if they can be eligible for part inhibitor. We want to look to see if their cancers are hurt too low. We're looking at the pick three C. A mutation status and increasingly we are also looking at the tumor mutation burden. And one of the important questions moving forward is now that we have these new treatments. What's the best order to go through these treatments. And again as you heard from dr delaney there are many ongoing trials across different lines of therapy next slide. So now I want to turn to metastatic triple negative breast cancer. And even just a few years ago this is how we treated patients with metastatic triple negative breast cancer. At first we gave chemo. The second treatment was chemo. The third treatment was chemo. Fourth or fifth or beyond treatments were chemotherapy. And we didn't think it mattered that much. Which order you went through which chemotherapy treatments. They were all conventional chemotherapy next time. But what has happened is really a lot of new developments in the management of patients with triple negative breast cancer. And I'm going to focus on trade LV. And in her too And I'll make some comments about immunotherapy but there are others that I won't be able to get to today. Next slide. So now this is what the treatment algorithm looks like. And you can see it's like more complicated. There are more drugs, there's more pathways there's more options. And it also means that we have to do more testing to figure out which is the best path for patients. So for the first treatment we test as you heard from dr delaney for this marker called PD L. One, which tells us whether the treat whether immunotherapy plus chemotherapy would be useful. So patients who are Pd L. One positive, we give chemotherapy and immunotherapy. If a patient is PDO one negative, we typically start with chemotherapy. But if they have a mutation in one of these breast cancer genes, we could give an oral part inhibitor as the second treatment we are often giving trade LV. Or societies ma'am. But in some patients were her too low. We might choose to give and her two first. And for patients who didn't get part inhibitor as their first treatment that could be considered then and then you do the flip around for the third type of treatment. So somebody had to be first. They might get uh in her to next if the cancers are too low or they might get vice versa or chemotherapy and then 4th, 5th and beyond treatments they exist and they are possible but they're typically at this point regular chemotherapy next slide. So just to show why these changes have been made into our clinical practice. This was a phase three trial to patients with metastatic triple negative breast cancer patients either got regular chemotherapy or they got trade LVS. A citizen lab next slide. And this just graphically shows the results of the study. The average time to cancer worsening shown in the blue with Saskatoon versus regular chemo in the red was much longer and the average survival with Saskatoon compared to regular chemotherapy was much longer. And remember these are all just averages. So many patients actually did better than the average. And finally the chance of tumor shrinkage was considerably higher with compared to regular therapy. That's why Um this is the other antibody drug conjugate in her to this is restricted to people with her too low breast cancer. So this is about 40% of triple negative breast cancer patients. Next slide. And again in this study now just focusing on patients with triple negative breast cancer enrolled in the destiny breast over for trial. Um as you see again in blue, which which is the TXT and her two group, there was a longer time before the cancer got worse and a significantly longer survival just seen in a small study of these patients but certainly very promising for the activity level of in her to for her to low triple negative breast cancer patients next slide. So for triple negative breast cancer. Again, more options. I've listed some of the things that we routinely like to do for testing including Pd L. One testing genetic testing, figuring out the her two status. And then just like Herman receptor positive breast cancer. Now that we have more drugs we'll have to figure out what is the best order to go through those medicines. And there's many clinical trials. Next slide. The final group I'm going to talk about is her too. And so the two drugs I'm going to focus on are in her two and two Kaiser or to catch him. I will just point out that there are a number of other new advances that you will hear more about in the her two session. But these include March March attacks or Morganza and then this three drug combination that was actually developed by Dr Delaney that is incorporating a C. D. K. Four inhibitor called Reason Neo in the treatment of her two positive breast cancer patients. Next slide. So why do we why do we changed our treatment algorithms. And so this is the first study is a phase three study which was looking at and her two versus our old standard which was T. DM one otherwise known as kat Zilla. And many of you may have received this drug in the past in this trial patients either received in her too or they received Godzilla as their second treatment for metastatic her two positive breast cancer. Next slide. And again just showing the waterfall plots you can see on top with the T. D. X. D. Almost nobody had worsening of cancer as their best response. Almost everyone had some degree of tumor shrinkage and the vast majority of people 80% had major tumor shrinkage. And this is in comparison to the T. DM. One group shown in the gray below were a good number of people had tumor shrinkage. However, there were larger number of people whose in whom it didn't work at all and overall patients were able to stay on the in her to longer than on the T. DM. One. And there was a trend longer survival at this early time point next line. And so this was approved by the FDA in May of this year. For patients who have her two positive metastatic breast cancer looks like. Um One of the important findings over the last year has also been that in her to a TXT might also work in the brain. And this is important because in the original phase three trial that I just showed you, patients who had active worsening cancer in the brain were not allowed to enroll in a trial. But now there have been at least three groups that have shown that T. D. X. D. And at least a small number of patients leads to significant tumor shrinkage in the brain. On the right is a is a picture of a patient treated at Dana Farber just showing the really dramatic um improvement or shrinkage in her brain metastases which is circled in the purple circle um with treatment within her two without the need for additional radiation therapy at the time that this area was treated. And so there is there are a number of clinical trials actually trying to use TTxT on its own or in combination with other medications in patients specifically with cancer in the brain. Next slide. Uh Finally, I want to talk about the her to climb trial. And this trial also took patients with her two positive metastatic breast cancer patients either received trustees MEB and keeps it to be so trustees member Herceptin with chemo or they received Herceptin chemo and the medicine to Catnip. I'll note that in the so called placebo arm, the placebo was for to catnip but everybody received Herceptin and everybody received chemotherapy next slide. And in this study the results showed that adding the two catnip to the Herceptin chemo regimen resulted in longer period of disease control, both overall in the body and in the brain there was a higher chance of tumor shrinkage, both in the body and the brain. And there was extended survival, including in patients with brain metastases where the degree of extended survival was really unprecedented compared to other clinical trials we've seen in patients with brain metastases. Next slide. So where are we now in metastatic breast cancer. I've kind of highlighted some of the important recent treatment advances in all three subtypes. If you want to hear more details, please join us at our next subtype specific sessions later this morning. Um and there you will also hear about many of our ongoing clinical trials testing new treatments. Next line finally, I want to make a few comments about our embraced program and all patients who have metastatic breast cancer seen at least once at Dana Farber offered participation in this program. Next slide. Um This is how we make it work. And I want to specifically call out the five individuals on the bottom left who are embraced coordinators and really do the work of tracking clinical trial matching, helping to organize specialized tumor testing. Working with your doctors and your nurse practitioner P. A. S. To really try to provide as as best care that we can to to patients seen at Dana Farber. Um we have integrated both the embraced clinical program and the optional research study that goes along with it. And we've actually approached almost 4000 people for the embraced clinical program since 2015 To give a sense of the scale. We've had over 2000 patients have agreed to have their tumor or blood tested specifically to see whether they might qualify for specific targeted clinical trials. And we facilitated what's called next generation sequencing testing in about 3000 individuals And many of you in the audience may have contributed blood samples to the embraced research study. We've now collected about 8000 blood samples and we're so excited about having this resource because it means that we can start really asking interesting and important questions about why cancers become resistant to treatment. Next slide we're also um launched a patient a survey for newly diagnosed metastatic breast cancer patients. Uh this is just an example of one of the surveys, but our goal for the surveys to try to understand where we're meeting patients needs and we're where we're not a successful meeting patients needs so that we can make improvements to the services that we offer this line. And then finally just a sampling of ongoing projects. One of the ones that we're really excited about for the next year is trying to understand our metrics um, by and and how we're doing according to race and ethnicity. As far as clinical trial enrollment and specialized testing. And we're also going to be rolling out a new program where we screen people for social determinants of health and there will be interventions that happen depending on patient's responses to the questions. And as I said, we have a lot of projects really from a scientific level trying to understand the mechanisms of resistance Next line. So I hope that you come away from this session and also those sessions later today with the message of hope that we are really trying to accelerate the rate of progress as much as humanly possible. And we really are, you know, hoping to partner with all of you to make the progress as as fast as we possibly can next slide. And so we're gonna move on to the Q. And A. And Leanne is gonna take over and again I want to just remind people to put questions that they have in the Q. And A. And we'll try to get to as many as we can. Yes so make sure you add those questions to the bottom. We've got a few already. Um dr Lynn I'll throw this one to you since you talked a little bit about um treatments for hormone positive disease. What you see to be the next big treatment for hormone hormone positive disease. Um looking at um with her to Herceptin was um made a big change in the outcomes for those patients. So what do you see for hormone positive? And is there anything like that? Yeah I think for hormone receptor positive the sort of two big categories one is can we better improve hormonal therapy. And some of the studies that are I think some of the important studies are studies that are looking at whether and how much advantage there could be of continuing a C. D. K. Inhibitor from one treatment line to another. So normally you know if you've been on a cycle of the cancer gets worse you come off of a cyclist and you don't start another C. D. K. 46 inhibitor. But there's some evidence that going from one C. D. K four inhibitor another or continuing might be beneficial. We don't know that for sure yet. But there are ongoing trials to really try to address that question. I think that's a very important clinical question because if we can try to make hormonal therapy work as long as possible that would be obviously a good thing. And then the next is just this whole category of antibody drug conjugate is because I just show you two of them true. Delvian in her too. But in fact there's like a whole universe of antibody drug huge hot topic and drug development and there are a number of antibody drug conjugate that are already in phase two and even in phase three trials. So I think that you know a few years from now we may be seeing even more antibody drug conjugate is both for triple negative and for er positive breast cancer. Thank you for that. Um Dr Delaney can you talk a little bit about when is a good time to do testing for changes within your tumor different mutations and specifically if you have been stable. Is there any advantage to testing and advance of progression to look to see if you can possibly prevent it or be a step ahead of it? That's actually a really interesting and important and sort of timely question because I think that's a question where we are trying to learn normally we thought that when a drug stopped working would be the ultimate time to test because it would suggest something's changed about the tumor And we need to figure out what's changed so that we can figure out if there's a better treatment strategy that would be specific to that patient's tumor. So for example if you were on a drug and it stopped working and you got let's say C. T. DNA checked and you saw that the C. T. DNA showed there was a particular mutation present. Then maybe it tells us we should shut down that pathway with a different drug to help at that particular time. So usually our stance is to think about re understanding the tumor either with sometimes getting a repeat biopsy or getting blood to look at C. T. DNA to see if there's a better approach. Um That's more specific to that patient at that time. But we are learning I think to your question is would it be advantageous to know this earlier? So if you were stable on a therapy would there be a way we could see resistance starting to emerge even before the scan showed progression. Could we track that even earlier in the blood for example. And could that help us figure out how to switch therapy even before the cancer grew on a scan. And in fact that is where a lot of research is headed because we do have the ability to look at circulating tumor D. N. A. Pretty easily. Right Because it's just a blood draw. Um could we do that while someone stable on their cancer and figure out if resistance is starting to occur. And there is actually an interesting trial ongoing right now actually trying to do this very thing it's called the serena six study. So it's specific to people who are on endocrine agent with specifically in a roman taste inhibitor with a C. D. K 46 inhibitor. So usually as nancy reviewed, if someone has hormone receptor positive breast cancer were usually starting them on hormone therapy with a C. D. K 46 inhibitor. But one way cancers can become resistant to that endocrine agent is sort of developing a mutation in the estrogen receptor where then it doesn't care if you've messed with. The estrogen level is just going to keep signaling on its own. And so our thought is well maybe if we knew that mutation was starting to come, even though the scans were stable then we could switch drugs. So we are trying this, we don't know if doing this is going to change long term outcomes. But it is a clever way to see if we could figure out if that resistance is emerging sooner. But it's not something we're standard lee doing because we don't know enough information at this time. But it is where a lot of trials are headed to do exactly that which was asked is can we screen even earlier, Let me have you, let me there's a question that kind of hooks onto this as far as like the use of um Let me see if I can find it. C. T. D. N. A. Um What is it busy? Um Is it being like regularly used in clinic? Is it a standard thing that's being done? Um and is their current research that is that anybody can participate in to help further the understanding and use of that? Um morality. Yeah. So this is of high interest to our group. One of our colleagues heather Parsons is actually leading a circulating tumor DNA program in our group where we do think that this is gonna be a path forward that is really gonna help us tailor treatment better. Um So currently from a standard perspective I'm usually thinking about it in particular situations but mostly in hormone receptor positive breast cancer because that's where we do have knowledge of a couple of mutations that can help us tailor therapy. And so I like to see that those mutations happen so that I can see if a particular drug would work. Currently there are fewer mutations that our target herbal in her two positive or triple negative breast cancer. But we are learning um And so things like finding if someone has a higher tumor mutation burden is really important to know if immunotherapy can work knowing if someone is a P. Three kind of mutation can help an ear positive disease. Knowing if someone is an E. S. R. One mutation may help us tailor to figure out with these new oral um anti estrogen agents. Um So I think understanding these mutations is important but I do periodically use it in air positive cancer. Um We do like to have genomics on all of our patients um to make sure if there are other alterations. And it turns out there there are some rare ones that are really important to know about specifically also for clinical trials. But you don't there's not quite as much data about getting them serially. We do like to at least have it once and then sometimes to repeat it again. But it is ongoing and research so dr lin may want to share. So I'll pass it off to you. But in the embrace program actually we do routinely collect circulating tumor DNA on patients if the cancer seems to be changing and before these people start a new therapy so that we can learn what's emerging but nancy I'll pass it off to you about the routine collections that are ongoing from a research right? So you know just to distinguish we are able to collect C. T. N. A. For clinical testing. We sent off to a commercial lab, you get the results back, your doctor gets the results back and that's what this little lady was was discussing um those tests you know usually sequence a couple 100 genes like the ones that we think are most so called actionable meaning if we saw change we might know what to do about it. But um we also collect blood for research testing for C. T. N. A. Where we can actually you know, sequence thousands of genes. And that's not something done is a clinical test currently. And the reason we're doing that is because for example Dr Parsons has a project right now that we're working on in patients who have had either to cognitive or neurotic or Lopatin. And one of these her two targeted drugs. And we have a blood sample before they started and we have a blood sample when the cancer got worse. And we're sequencing both of those samples. And then we're trying to see what's changed between the original sample and the new sample that might explain why cancers became resistant to that treatment. And the reason why that's important is because if we can figure it out, maybe we can develop drugs to actually prevent that resistance from happening or treat that resistance mechanism. Um and I will just acknowledge that you know people uh you know people who have provided blood samples and embrace, we have projects for her to that are ongoing. We have this very large scale project to try to sequence patients who have estrogen receptor positive breast cancer who have donated C. T. DNA samples for research. Um And we're we've already published on some work with triple negative breast cancer patients in the C. T. D. N. A. And in fact the whole idea of C. T. DNA. Technology and breast cancer. Um Some of the samples from the early early patients who went on embrace were actually used to develop some of the technology. So I mean it really you know when you get these extra blood draws you noticed like extra tubes being taken at the time of scans um you know these these extra tubes have actually generated incredible impact and impact that's now used in regular clinical setting but also impact as far as how we're going to learn more about cancer. Um Not a surprise but there are a lot of questions about her to um so you know start with um kind of what are the side effects that you're seeing within her to um what effect are they having on patients And then to link with that. Um What kind of what are you seeing as far as quality of life um with patients um And these new drugs and how are you guys managing that? I'm happy to start. So I mean I think first as nancy showed the data for and her to um is really I think very exciting and groundbreaking. Um You know we had seen originally this drug work for her two positive breast cancer tremendously well and it is a standard agent for that sub type of breast cancer but now it's also available for patients who have heard too low breast cancer as nancy was alluding to, meaning that they just have a little bit of her two expression, even though it's not a her two positive cancer, which, you know truthfully over half of breast cancer. So it's a large number of patients where this is an option, which is I think really exciting. It certainly does have some side effects. Um So while it is an antibody drug conjugate and it's trying to deliver the chemo right into the cell. There are some side effects from it. One of the more common side effects is nausea. Um And so we do have to give some anti nausea medications just prior to the infusion to try to prevent that nausea and actually works pretty well. Um When we do that, sometimes people do still have nausea though. And so we do um you know use periodic anti nausea medications over the timeframe in between their treatment. So it's every ivy every three weeks. And so sometimes people are needing periodic anti nausea drugs through that course, but we learn how to work through that. It can cause some fatigue. About 10% of people will completely lose their hair from the drug. We are actually studying to see if scalp cooling can help prevent that at our institution. Um And so there's a trial ongoing looking at that, which is nice so that we'll be able to learn more. The one toxicity that we're we are a little bit more cautious about is a risk of what we call interstitial lung disease, meaning that it can cause inflammation in the lungs, which could make someone get short of breath or have a cough And sometimes it's just very mild and in fact, you know, it's about 10% of people that get this interstitial lung disease and most of the time it's mild and in fact often times it's just something we pick up on a scan that the patient actually didn't feel any symptoms from. But sometimes it could be more serious. And so because of that, it is really important that we do carefully monitor people for this. Um and that if it happens, we do have ways to treat it with steroids which can decrease the inflammation and things usually turn around. The problem is is that if the interstitial lung disease is present and someone has symptoms from it, we actually have to discontinue the drug Because the worry is that it could lead to more serious um long toxicity. So that is again, it's 10% of patients, but it is, you know, a more serious side effect that we do have to monitor for. But you know, in terms of the question about quality of life, they actually just presented some data on this at our, one of the international meetings that asthma just a couple of weeks ago where they actually had patients report out there own you know, symptoms over time and compared it with people getting in her to to standard chemotherapy and in fact quality of life was better in the patient's getting in her to compared to standard chemo, you know, oftentimes that's because people are responding so well to therapy that a lot of their other side effects from their cancer gets so much better that they are feeling better. And in fact it was their symptoms were controlled for much longer and people getting in her two compared to standard chemotherapy. So I think that's reassuring that even though these drugs do have side effects that patients actually did very well with it. Let me just follow up with that when you speak to chemotherapy versus something else. Or is chemotherapy always a an infusion or can it be an oral drug? Can you kind of That terminology is a little kind of confusing I think. Yeah. You know, we think of in terms of the classification is a little confusing because you also may hear somewhat different things from pharmacists or others, like a lot of people involved in cancer care and people might categorize things differently. And the way I think about it is chemotherapy is um is what we call cited toxic drugs. So they directly affect the ability of cells to divide usually through some process related to DNA replication and cell division. And so chemotherapy drugs could be like Taxol or remission but they also could be solo to which is an oral chemotherapy pill. So it's not categorized based on how it's given. It's categorized by how it works. Whereas targeted therapies are things like hormonal therapy which target the estrogen receptor or C. D. K. Four inhibitors which target C K. Four and six. Um And then immuno therapies are medicines like embolism ever keytruda which are are designed to stimulate the immune system function. So you know there are different categorizations can be a little bit confusing because sometimes people don't categorize everything exactly the same. But definitely chemotherapy can be both oral and I. V. And let me just follow up on in her to what do we know about in her two and left a man in jail disease. Um That's a great question. We know a little bit um like a little more than we did before. And we have a manuscript that's actually under review right now where we looked at eight patients treated. I mean it's very small numbers right? But we looked at eight patients treated between Dana Farber and Duke University Cancer Center. And we did actually see um patients benefit from in her two for leptin potential disease. You know we didn't know ahead of time whether we would see that because it's a big molecule and we didn't know whether it would get into the spinal fluid well enough. But um at least preliminarily it looks promising. And we're hoping to put together a trial actually for patients who have either her two positive or her too low disease within her to over the next year. You know, we know how important the data is from clinical trials and obviously we need people to participate in those trials in order to get that data. So from a patient perspective, when it comes to decision making about standard of care versus clinical trials feels overwhelming, how do they make that decision? Um you can one of you maybe dr delaney? Yeah, no I think it's a really important question and you know, certainly I think clinical trials have a lot of advantages but certainly there are some disadvantages, you know, I think and I always try to review the pros and cons of each situation in a particular point in time with the patient. So, you know, usually at the point of time to think about a trial is when the cancer is growing on occurred treatment. So when that treatment is not working anymore and you're ready to move on to something next. We're usually weighing what the standard options would be with a particular clinical trial option at that time. And then we're trying to weigh the pros and cons of of each approach when I think about the clinical trial. You know, it's important to understand um sort of where that drug is in development, what's been seen with the drug. How effective has it been and how effective do we think will it will be for that individual patient, what the potential side effects are, how often the visits are because sometimes some trials are earlier in development where the drug is newer and because of that there's a lot of extra tests sometimes that are required. Sometimes their blood draws to look at drug levels. Um So they're more visits that are required to get those drug levels more assessments because we need to make sure their patients aren't experienced side effects. So you have to see if it's practical too for the patients, someone lives you know four hours away and the visits are so often and it would really be very challenging for them then that's you know an issue that we have to think about. Um But the advantage is that you can get new highly effective drugs so much earlier um and to me that's tremendous. It it gives you access to new drugs but also it opens I think of it as like a menu of the different choices that we have to choose from. It makes your menu longer right? Because you not only have the standard choices, but now you're adding in all these new drugs that we can integrate along the way. And so to me that's a huge advantage. Um And so you just have to figure out at the right time, you know at a particular circumstances if that trial is right for the patient or not And and it is, you know, I totally agree, it can be overwhelming. Um but I do think, you know, an important discussion with your physician who will be honest with you to weigh those pros and cons with you is really the best way to make that decision. And I would just also add that, you know, I think choice can be overwhelming. And so in general I try to sort of narrow down like this is the best trial I can find or maybe the best one or two trials I can find. And this is what I would recommend outside of a trial so that people are not trying to make research like a universe of 20 options, which is just totally overwhelming. And and I think that's where your, you know, oncologist hopefully can be very helpful and kind of narrowing things down so that it becomes a more um kind of two options or three option choice, which I think is much more, much more doable. And then I Leanne, you're moderating so you're not answering the questions. But I'm gonna ask you to answer this question because I know you've been really involved in efforts to try to link patients to clinical trials. And I wanted to see maybe if you could comment on that. Um I mean I'm a huge fan of clinical trials, I've done clinical trials that have both. You could say we're successful, meaning the drug worked for me. Um and then even when the drug didn't, there's an initial feeling of like, oh man, but I realized that that helps the oncologist and the research um And no kind of more about the drug, even though it didn't work for me, and I think about where we've come, if you look at the drugs that were available just even 10 years ago, the drugs that I'm benefiting from now, the only reason that I got to participate and got those drugs is because someone else chose to be in a clinical trial. So I looked at a little bit like payback, like, you know, I'm helping move that needle forward. Um but um I think obviously, you know, it's really important to talk to your oncologist about um I think very upfront in the beginning stating that what your interest is in clinical trials and that, you know, keep that open dialogue. That's so important that they know what your feelings are about those. I think that's a really important point also about talking to your oncologist upfront because I think some people think clinical trials are not to be used when there are standard options. I think maybe you only do a trial if there's not a good standard option, but in fact, I think it's almost the reverse that, you know, at any point in time, um you know, there are clinical trials all along the way, Sometimes they're just adding an extra drug to the standard drug, you know, and it it's just adding more in fact, rather than something else. So I think again, such an important comment that right from the very beginning, um knowing what your options are. Both from a standard perspective and from a clinical trial perspective is important. Yeah, I agree. You know I um I was one of those persons that at the beginning I could not understand why I would pick the unknown over the known because my first line of treatment was a clinical trial. And once I sort of got a little more information from my oncologist and learned about what actually can be the advantage of clinical trials. And I did I got a drug that um was not FDA approved yet. It was very successful for me. So I learned very quickly how advantageous they can be. Um Yeah, so I think we're I think we're running a little short on time. Is that right? You can see you may be on mute. I think we have about five more minutes so we can not only a couple more questions and then there's a closing slide just to help people figure out which way to go to morning timing. Um jump back up here. So, um how do you go about finding clinical trials since we're talking about them? What's the best way to find a clinical trial and know that it's right for you. So I'll say this is a topic near and dear to my heart, you know, I ran our clinical trials program for a number of years and wanted to figure out ways, not only for the patient to figure out the best trial for them, but also for the physician because we have so many trials. Um and now as you saw, the biology of everyone's cancer is getting so complicated, you're looking at what mutations they have, if they have a particular protein, how many treatments they previously had and like you have to factor all these things in to figure out the best match. So our group actually created a clinical, like a program. We had a computer. My husband actually programmed this thing for us where we can plug in all the information for a particular patient so that we can factor in what, you know, is there a mutation, is it er positive or the pd L one positive? Do they have a mutation? Do they have two prior lines of treatment, all this stuff? And then the computer spits out what the matches are because again it isn't quite so straightforward and you know, I think when patients, I have patients who like search online, there's this site, you know, the clinical trials dot gov where we have to input all our clinical trials into this site online. But also even as a physician navigating that is really hard, you get all this stuff and most of the trials like they're not exactly the right fit um for the patient because again, you have to factor in so many different components. So I think it should not be on the patient to be sorting this out at all. I think it is very complicated. Even again complicated for physicians and I really think this is such an important conversation with your oncologist because they can help you figure out what trials do make sense and you know, well it's true that you know, you're going to see an oncologist at a particular cancer center. So let's say you came to Dana Farber, we obviously know our own clinical trials in and out. Um, but I think sometimes people wonder, well what about a trial that maybe somewhere else that isn't at the site that I'm going to, how would I figure out if maybe there's a better, if it's somewhere else. And usually as an oncologist we typically know kind of what drugs are gonna be good in a particular setting. And so even if we didn't have that trial, I often will know who does have that trial. And we can usually email our friends at another site and say, hey, is there a slot on that study? And so, you know, I'd say put that burden on your oncologist that is not a burden for you to carry to navigate this? This is something they should be doing for you and help you find the right match because it is so complex and I think can be very overwhelming and the stuff online can be just again, even overwhelming for a physician. So I think again this really is your oncologist to help you guide you here and I think that you know what's also very helpful is to is the communication right? So if somebody tells me I'm willing to, you know, let's say they live in maine, I'm willing to go down to the Morrison encountering in europe for a trial. If you don't have a good trial for me or I want to know what the universal trials is, you just have to ask but you know because there are so many trials that so many centers and there's many centers across the US, like it's actually not very practical to look at every single trial is available in the entire United States for that specific patient. The output is very, very long. But if we never get down to a few locations then that's very doable and we do that all the time. We just the patients need to communicate. So I think again like this will, you know, stress the communication right? Like if if you live four hours away but you're definitely willing to come down for a trial, don't let your doctor assume that you're not going to be interested in a trial, like tell them you're interested in a trial and then they'll know um and if you are in an academic center typically that's where, you know, most of the kind of earlier phase studies are, are centered. So also phase three studies often will be at lots of lots of different centers across the United States or around the world, smaller centers, bigger centers, community centers, etcetera. But the phase one or two trials most frequently are going to be found in the academic centers. And so if you are seeing in a community site, you know, most places including us will be willing to partner with your community, you know, local oncologist to see you periodically um to see whether or not at different times when your cancer is worse, where you might qualify for trials at that time. Yeah, I would just echo that that the communication with your oncologist is so important, what you're willing to do what phase of trial and that's even if you don't understand the different phases, having that conversation in general about what clinical trials are. You know, that should be something that you're oncologist is willing to talk through with you so that you're both on the same page and overall just having that sort of open dialogue about everything that you do with your oncologist. Um in addition to in her to um this person mentioned, they developed um lung issue on in her too. And what other adcs are coming down the line and do they also have the issues with lungs or um can you maybe speak to that? So there are I think the exciting thing is there are lots of new antibody drug conjugate is coming along and which I think is tremendous. Um There are some that do not have this risk of long toxicity but unfortunately there are a couple that that also do. And we have several trials that are open with novel antibody drug conjugate. Um One can mention a couple of them. One of them is a drug called all these names are quite terrible but they're also called data D. X. D. Which is what I call for short. Um It is another antibody drug conjugate that's targeting trope to kind of like the society is a map of a tickin drug is um And it's early data shows really impressive responses. They haven't seen much interstitial lung disease so far with that drug. So that is reassuring. Um And really is being tested in both triple negative and hormone receptor positive breast cancer. And and looks again very very high response rates. It looks great. We also have a drug called RX788 and which is a her two directed antibody drug conjugate. It's being studied in people who have already had in her two or two catnip and then it it can be utilized that does have some interstitial lung disease with it though. Um And so you know that is a potential toxicity but there are more and more of these antibody drug conjugate that are coming And in fact one of our colleagues is going to be running a trial to answer how to optimally sequence these drugs because now that we're getting to have so many I think one of the things we're not so sure about is does it matter what order you give them in and can they work one after the other because some of them do deliver the same chemotherapy and is that going to work even if they're targeting something different? So we need to learn more and we will have a trial coming up that will look at giving one of these drugs after the other and then doing vice versa switching the order up. So I think we're going to learn more and more about these drugs. Oh yeah and I think you're on mute. That's how a lot of people would prefer. Um No I just wanted to there are a lot of thank you's in here for the presentation today researcher patients all just commenting on how grateful they are for the work that you to do. Um And um everything that's that goes into putting on this presentation and that could be in condition and lots of things a lot and thank you. So I'm gonna have melissa show the last slide now we'll wrap up. So thank you again for joining us today. We're really happy that you could join us early in the morning on on a saturday. I know some of you are probably on the West Coast and even earlier in the morning. So thank you for waking up to to to join. I just want to walk you through um the the breakout sessions that will be happening later this morning for those who already know what subtype of breast cancer you have. You would just go to the subtype specific session but just to give us a hint to people who are maybe not so sure if you've ever received Herceptin, Pirjeta Godzilla or take ISA, you most likely have heard two positive disease and you would go into the her two positive session if you have not received any of these drugs but you've received one of these hormone therapies like tamoxifen or Elektra's all Arimidex or excess stain. Or if you've received a C D K 46 inhibitor you most likely have estrogen receptor positive breast cancer. And if you haven't received any of these drugs, most likely you have triple negative breast cancer. A question that comes up frequently is what if I had one and it switched to another were usually treating patients based on the most recent biopsy. So if you were estrogen positive and now you're triple negative probably the the triple negative session is the right one to go to. If you go to a session and you realize later on. Oh I really wanted to go to a different session. All of the sessions are being recorded and once they're edited and produced they will actually be posted on our dana Farber website. And we are planning this year to email links to the presentations to all registrants for the embrace virtual forum series. So there'll be other opportunities to look at it, especially if you feel like you want to watch something again or you wanted to watch about a different subtype. So with that I wanted to see if Sarah wanted to say any final last words and we'll wrap up this opening session first. I just wanted to thank all the people involved in really putting this together nancy in particular who really has spearheaded um putting together really creating the whole metastatic breast cancer program at dana Farber and then creating this series for patients, which I think has been um as physicians, we also enjoy it. Um so thank you so much for for all the efforts. It's really amazing to see how much patients also give of themselves to be able to help us learn how to make outcomes better. So thank you to all of you also for all that you're doing for research and improving everyone's outcome. So thank you all And thank you liane for moderating. You did a wonderful job as always. It's always such a pleasure to work with, you know, my pleasure, thank you for the invitation to do so I almost had it all in use on and off. Just great. Well thanks everyone for joining us and the sessions resume at 11:30 PM time today by.