[Music] the primary goal should be trying to figure out what causes breast cancer and what can we do with the immune system to prevent it from happening at all imagine a world where breast cancer deaths are a thing of the past thanks to revolutionary vaccines designed to treat existing cancers or prevent them from making a comeback the promise of cancer vaccines that's what we're getting into in this episode of tomorrow's cure a podcast from Mayo Clinic that brings the future of medicine to the present I'm Kathy warer thanks for being with us we have a number of guests with us today they include researchers who study cancer as well as oncologists who treat patients Dr Sarah chumsri is joining us from Mayo Clinic she's a medical oncologist and professor of oncology also with us from Mayo Clinic is Dr Keith kuten he's a professor of immunology and professor of cancer research Dr Ken's research is aimed at preventing patients with cancer from relapsing after they receive conventional cancer therapies and finally medical oncologist and researcher Dr Nora diesis joins us from the University of Washington where she's a professor of Medicine Dr Deus is also director of the U medicine cancer vaccine Institute and a member of the Fred Hutch Cancer Center really a pleasure to have all of you with us thanks for being here glad to be here good to be here yeah thank you for having us you know I have found that there's usually a story behind why a researcher focuses on a specific area of study or a topic and I want to know what's the story behind your interest in breast cancer I'm going to begin with Dr kutson so it's a little bit of thought and a little bit of serendipity uh so uh I actually started off training as a molecular pharmacologist at the University of Georgia and then switched gears and went to the University of British Columbia as a molecular immunologist and I was uh fortunate enough uh having wanted to stay in Immunology uh to find a position actually in in uh norisa laboratory back in uh the late 1990s and so we it just had so much going on and and so much interest in in developing vaccines and and studying you know the role of the immune system in breast cancer that I couldn't leave after that I just needed to stay in that area so Dr D say you helped launch Dr Canon's career good for you it didn't need much launching he was already a rocket see what's your story how' you get into breast cancer research personal it was somewhat personal I mean to be honest with you I came to Seattle as an oncology fellow and at the time I was the only woman uh in the fellowship class so when it came time to figure out what my clinical duties were going to be um I got assigned to the breast cancer clinic with a breast cancer Mentor because even at that point most women felt more comfortable with a woman medical oncologist and when I was uh in the lab we were trying to figure out really the major question at that time was was cancer even immunogenic could cancer stimulate the immune system so I would go to clinic with all kinds of blood tubes in my pocket and I would ask my patients in the clinic if they would give me some of their blood so that I could study whether they had immunity to their cancer and literally I ordered tumor cell lines from a company mashed them up and then ran their antibodies against these tumor salines to see if they had antibody responses and through that process I realized that so many of these women were my age they were in their 30s early 40s just slightly older than I was at the time and when you hear their stories they'd come in with very Advanced stage cancer and be like all I want to do is see my kid graduate from high school all you needed to do was hear them what their desires were so simple desires that we take for granted you know within a month I'm like I'm dedicating my life to trying to get rid of this disease and that's how it all came to be oh I'm glad you made that decision Dr chre I'm wondering what made you want to focus your research and your clinical work on breast cancer um I always kind of interested in immune system for quite some time like even a while back but then you know back then there was not a whole lot of you know um with the um immune checkpoint inhibitor immunotherapies um during my fellowship training and then my early career and then um I I was so fortunate to be able to move to um Mayo Clinic like back in 2014 and that's when I found Dr kutson like in his lab and I got so excited about you know what we can do with the um cancer vaccine and also immunotherapy in breast cancer I feel like this is you know kind of like the future of um cancer um treatment you know with the using harness um the immune system to fight off the cancer and you know like immune system is like a living drug right it's like the the um living treatment that can change and you know evolve uh with cancer cancer is just so smart they keep mutated and change over time and then you know with the same treatment that we focus and Target on one little thing it's just too smart that you know they're going to mutate and change and um you know find a way to grow around it so that's kind of really got me like so excited about the you know like this um immunotherapy and then uh collaborating with um Dr kson with the cancer vaccine just you know uh making me uh really happy and I love what I'm doing I can tell I can tell I can hardly wait to dive in to what you all are doing but I think we might want to take just a a step and look at where we are right now when it comes to breast cancer in this country and Dr kuden I don't know if you saw the Washington University School of Medicine study out of St Louis the diagnosis of breast cancer has increased steadily in folks under the age of 50 over the past 20 years and there are steeper increases in more recent years what do you think's going on well that's a that's really a great question um we wish we knew what caused breast cancer aside from you know a small percentage that are familial we understand that there's a number of mutated genes that may uh contribute to or that do contribute to the risk of of developing breast cancer um as to um you know what causes all of the other breast cancers that are you know not related we've been really scratching our heads and and really in the laboratory working hard we've been looking at viruses a number of different you know compounds that are uh in the environment uh the genetics of an individual and you know how that may contribute to you know abnormalities that uh occur um so uh we just don't you know um have an answer for you know why uh we we're seeing this you know increase in breast cancer particularly in um young individuals it's very alarming obviously but when you think about you know the the you know deaths that occur the cost of Health Care the the cost of grant funding the C the the costs of you know the loss of life and productivity you know you're talking hundreds of billions of dollars per year just in the us alone that um you know we spend on breast cancer um and I think that the you know uh the the primary goal should be trying to figure out what causes it and trying to figure out ways that we can protect and one of the things that we've been thinking about and what Nora and and uh Sarah have been thinking about too is you know what can we do with the immune system to you know uh protect against the development of breast cancer to prevent it from happening at all uh because once it happens then the challenges start to occur at least in some patients with health other health problems you know I am so honored uh Dr dies that you're with us because I was doing some reading on your background and about 20 years ago you had this groundbreaking idea that it's possible to harness the immune system to identify and treat cancer what led you to that light bulb moment well I think um 20 years ago we already knew some cancers were immunogenic like melanoma kidney cancer um but the thinking of the field was those were the only cancers that stimulated the immune response and they were very unique in being able to do that um we now know that these are the types of cancers that have lots of mutations they're more aggressive cancers but those mutations that accumulate in those cancers uh can actually stimulate the immune system because those mutations are seen as foreign by the immune system in uh diseases like breast cancer most colon cancers prostate cancer these are not highly mutated tumors but they do stimulate the immune system it just took looking at it in a slightly different way so for example instead of trying to detect the most important immune cells te- cells directed against the tumor I started looking at antibodies and patients had lots of antibodies directed against different antigens in the tumors unfortunately an bodies don't generate the type of killer te- cell response we need to eradicate a tumor or kill the tumor but it was a good Beacon to let us know that it is possible for these low mutation tumors to stimulate the immune system would you mind giving a Layman's definition of immunogenic yeah IM immunogenic means the ability to stimulate the immune system so an immunogenic protein in cancer has the potential to turn on the immune system when you develop a vaccine you have to immunize against something you know there has to be a Target that you're directing your immune response to and that Target is those immunogenic proteins Dr Chum you have been quoted as saying that you think the future of cancer treat is immunotherapy can can you expound on that a little bit as I mentioned earlier cancer it's really smart at some point when you targeted them with you know certain um you know treatment that Target certain pathway of the cancer cell it's going to eventually figure out and mutate and find a way to grow around it and we've seen that in with multiple um types of um targeted therapy um and on the other hand immune system like what Dr disis was mentioning you know like once you activate these um te cells or like B cells antibody response um these tea cells um you know basically like it's like a living drug that stay in your body right and then um it can um also has the ability to evolve um with the um you know cancer too but I think the tricky part is trying to activate our immune system to be able to recognize that particular cancer um it's different in different type of cancer like Dr D was mentioning I think in breast cancer may be a little bit difficult for the IM system to um you know generate the effective immune um response but think that's what we all try to work for so vaccines are a type of immunotherapy right so let's talk about some of these vaccines for breast cancer that you're you're all working on Dr canuteson I know you're in trials for a vaccine that focuses on three kinds of breast cancer so remind us what those subtypes are because I think that might be nice to run those down for listeners yeah so uh so we have variety of different clinical trials that uh cover uh different subtypes of breast cancer we think about three kinds of breast cancer we think about um you know estrogen uh receptor positive or hormone receptor positive breast cancer which is about 70% or so of uh breast cancers that are uh diagnosed and then uh the remaining uh fraction of breast cancers are kind of split into uh what we call either herto new positive or triple NE negative breast cancer and uh we have uh you know vaccine trials that are ongoing now targeting triple negative breast cancer as well as her to new positive breast cancer as well and we hope to and you know something that's been lacking and this is due to uh really the difficulty of being able to test this in in the clinic is trying to develop vaccines that Target uh hormone receptor estrogen receptor positive uh breast cancer because uh you know um when we we think about you know the possibility of preventing relapse those cancers tend to relapse you know 10 15 years in the in the future and so much of the work has focused on the other subtypes of of uh breast cancer because the relapse rate is much sooner and something that we can you know comprehend um you know on a shorter time you know scale than something like estrogen receptors when I first met Nora there wasn't a lot for her to new positive breast cancer and it was typically you know thought to be this very aggressive and it was aggressive uh some type of breast cancer but the fact of the matter is treatments have come a long way for this subtype of breast cancer and patients you know hardly ever recur um uh in general uh from her to new positive breast cancer and uh we know the patients we have great idea about uh ideas about which patients are going to recur and we're trying to you know Target those patients that we think are have a high risk of recurrence so there's still a few that do have that high risk and we're trying to identify what those patients are so a broad range of clinical trials uh and using more uh you know up-to-date information as to how to Target those so that we can show that the immune system can have an important impact uh on on recurrence um listeners I'm sure are familiar with something that you mentioned triple negative um I know that that is a very aggressive breast cancer and Dr dies I'm curious as to why it's so hard to treat triple negative breast cancer well in the past it's thought that triple negative is harder to treat because the treatment isn't prolonged so if you saw um her to new therapy the her to new positive breast cancer patients would get treated with chemotherapy and then monoclonal antibody therapy and they would go on to continue the monoclonal antibody therapy for a year after the end uh their surgery so this is called adant therapy so there there was very good adant therapy to mop up all the remaining breast cancer cells the same thing for hormone receptor positive cancer the patients may be treated with chemotherapy but then after surgery they end up having um hormonal therapy and that is an agement therapy that again suppresses the rec Ence of their breast cancer but there wasn't anything like that for triple negative breast cancer basically patients would be um treated with either chemotherapy or surgery and once that was over there was nothing left to do so that lack of adant therapy to mop up those remaining cells that might have become systemic resulted in a significant number of recurrences is in triple negative breast cancer but I do have to say the landscape of triple negative breast cancer is changing and changing dramatically so for example when I first got into breast cancer research and I would go to meetings and I would talk about the immunogenicity of breast cancer I'd have people you know get up and say why are you studying breast cancer why aren't you studying melanoma but yet now in the span of one person's career we've gone from people saying breast cancer can't even stimulate the immune system to a standard of care treatment for triple negative breast cancer is stimulating the immune system immunotherapy we now know that triple negative breast cancer is probably the most immunogenic type of breast cancer so I think um much like the landscape of how surviv of her to new positive breast cancer has changed I think we're going to be seeing some big changes for triple negative breast cancer as well which would be good news right especially for women of color uh especially for women of color young black women and uh uh latinx women are more likely than any other racial ethnic group to get triple negative is that right uh that's correct what do we know about that why might that be the case we don't really know what caused is breast cancer whether there's some genetics that are specific to particular populations that predisposed to a specific uh type of disease one of the things that we know when we're seeing breast cancer earlier in younger patients is that obesity is becoming an epidemic in the United States with almost 40% of the population uh being labor as obese uh by 2024 uh this year and we know that obesity um in fact you know having a very elevated BMI in the obese range is a risk factor for developing certain types of cancers such as breast cancer prostate cancer endometrial cancer so one of the things people are really thinking about is being a lot more aggressive about educating on diet educating on the importance of physical activity in terms of decreasing obesity and potentially reducing a very important risk factor for some of our most common cancers we know that obesity kind of increased risk of breast cancer because these you know um you know the amount of the fat cell does generate um quite significant cyto kind it lead to inflammation so I think um you know educating that and try to reduce the incidence of um obesity can potentially help prevent um cancer not just breast but um a lot of other type of cancer that associated with obesity interesting say I want to bring it around to vaccines for just a moment if I could now we already have two vaccines to prevent uh diseases associated with um cancer right HPV for cervical cancer and the hepatitis B vaccine for liver cancer and those are associated with viruses how is the approach a little different perhaps with breast cancer are there similarities are there differences Dr kuden well you know so there may be some similarities so for example um Nora had alluded to O obesity and there's a strong link with inflammation so you know what we think with respect to uh cancers that are caused by uh the human papiloma virus or the Hepatitis B virus is that uh there's this long you know drawn out chronic inflammation and chronic inflammation is associated with the development of malignancy and so that maybe you know uh one uh you know place to look at for a possible cause for developing breast cancer and then things that cause chronic inflammation can lead to the development of breast cancer but uh the um you know the general thinking is that you know there's probably something like uh you know a chronic inflammatory event that's leading to uh this uh you know generation of these malignant cells in the breast uh but Studies have been done uh repeatedly throughout the years and it's it's all it's always difficult to say that we'll never uh you know find a virus that's associated with breast cancer I don't I'm not sure that there ever will be I think when you look at HPV or or hbv vaccines they've got a big leg up and that is they give a danger signal to the immune system these are germs and the immune system was developed specifically to protect us from germs so when you put a germ into the body the immune system brings everything to bear in taking care of getting rid of that pathogen so when you talk about cancer you would love love to have immunogenic proteins associated with cancer give that same danger signal mutated proteins they can be seen as dangerous to the immune system when you think about a cancer growing really fast like a growth Factory receptor like her too it's expressed at very high levels so it's weird enough that the immune system thinks something's not quite right here but it's self enough that not only does the immune system not attack it it sends a signal to try to repair the cell fix the cell and some of the cyto kindes or substances that are generated by a certain type of immune cell called nade immune cell actually helps the cancer to grow so people developing vaccines their first thought has got to be the antigen the immunogenic Protein that's going to be in the vaccine like the covid protein covid gives a great danger signal so you don't need much to get a super great immune response but the less and less immunogenic those proteins are the more and more you're going to have to engineer the VAC seen in other ways to give that danger signal say um I'm curious can I bring it around to something you mentioned about chronic inflammation how would you know how would someone know if they're at risk for chronic chronic inflammation studies over the years have really you know told us what causes chronic inflammation um so for example smoking cigarettes cause causes chronic inflammation in the lung causes mutations in the lung and that ultimately leads to the development of poignancy and in other cancers as well colon cancer for example we know that chronic inflammation leads to um the development of cancer as well say Dr kuden the vaccine you're developing how will it be administered is that going to be a one anddone injection is it boosters might they be needed what are you thinking well we we you know so we have a number of different roaches that we're using um you know so for example we have peptide vaccines that are administered with this danger signal so that we can alert the immune system to respond and you know those are given periodically uh much like other vaccine strategies to you know uh generate the immune response now one fascinating feature about the immune immune system is that it has the capability of generating uh immune memory and so really That's the basis for uh vaccination so uh some vaccines depends on the platforms require some boosters and those are uh you know just you know sometime in in in the future you will have to you know have a restimulation of your immune system to you know increase those B cells increase those uh t- cells some vaccines there's no need to give a booster those are the kinds of questions that we're asking now or is the initial series of vaccine good enough like it is for some other diseases uh say because you all are involved in studies and trials Dr chumsri I'm wondering you know you said that young black women in uh latinx women are more likely than other racial ethnic groups to be diagnosed with a triple negative breast cancer when we look at some of the studies around uh different types of breast cancers uh when it comes to clinical trials do you think that um there is sufficient ra and ethnicity diversity in some of these trials and if if not how does that how does that change yeah I think that's a a lot of efforts coming out to try to increase um patient diversity um and role in the clinical trial and um as you eluded to I think that's been a a global problems like if you look at you know even large randomized um uh control clinical trials across the globe with multiple countries um those countries that participate in the trial in up being you know mainly in the North America Europe and Australia um me you know like um African-American patients are under represented um you know and and Latino patients are under represented but um there are a big movement on you know trying to improve upon that um you know increase the the site that we'll be able to enroll more minorities into our clinical trials but it's very quite challenging and we're not reaching out the patient population that need us these clinical trial moves I think there's even a more fundamental question than that uh when you look at it less than 10% of all cancer patients enroll on clinical trials so we're talking whether you're a minority or not a minority people don't enroll on clinical trials fundamentally a clinical trial isn't an is an experiment and it's a choice and so how many people are going to volunteer to be part of an experiment and I think that this is where scientists have to do better to communicate to people and to let people know that there are layers and layers and layers of um regulatory agencies that are ensuring the safety of those clinical trials but I can say honestly when you look at basic science or all the science leading up to the development of cancer vaccines we are moving at the speed of light and then bam we hit clinical trials and it's like a freight train going off a cliff all of a sudden the speed of research goes down to a crawl and that is because it's just incredibly difficult to get patients to volunteer to enroll on clinical trials and if you enroll a patient correctly you're telling people I don't know if this is going to help you this is a first and man you know study of a cancer vaccine with all my experience I can tell you I'm pretty sure it's not going to hurt you but when people volunteer many want to guarantee that this is going to benefit them in some way and we just can't give that especially for early stage clinical studies so if I had a magic wand or if a genie came and said you can have any wish about your research program what would it be I would say make clinical trials go faster and that means try to figure out a way to get more people to volunteer to be on clinical trials so help me out here right you mentioned you you just you clip along it's exciting and then it's like as you say the freight train goes off the cliff so what's your pitch to these women to become involved in these trials I would say that the pitch is look and it's not just to women it's to everyone sure we're all in this fight against cancer and when I hear people say somewhere someone's got the Cure and they're holding it back it just makes my blood boil because I'm in an institution that is just crammed with people working their fingers off trying to figure out how to end cancer so there's an army of scientists trying to figure this out but we need a citizen Army you need to join us in the fight not be passive we need volunteers to test these treatments so be part of our team be part of the process and then we can get to the end of this disease quicker say this podcast's title is of course tomorrow's cure and so I'm going to ask this final question what do you think the next Frontier is for this work so I think the future fun here that I really want to see is what Dr D was um mentioning that too like um is um to prevent breast uh to prevent cancer entirely I think in the future if we can have some form of you know cancer prevention cancer interception preventing cancer with the vaccine um you know I I think that's a big thing and I I hope to see that in my lifetime you know what's incredible now and really what the next Frontier is is our capabilities of interrogating human biology it's just absolutely incredible with all of these you know new uh um you know uh you know AI systems and and all kinds of big data sets that we can move through so we thought about uh another vaccine strategy that we have is ovarian cancer and thinking about you know how to you know how you know what we can develop and how we can develop and so we have to you know wait for data that came in slowly from humans to try to tweak our back so that it would work in humans and I think it's working pretty good but you know this is what took 15 years to um to try to understand just because the technologies that we had at that time were very slow now we have the abilities to sequence deep um you know much more cost effectively and much more rapidly uh both RNA and DNA uh we have all kinds of different uh multi-parametric to use a fancy scientific term there uh strategies to really interrogate what's going on in a human because that's really what's going to inform us when we move back into uh the laboratory to design and so the biggest Frontier is to be able to use all these you know new um you know computational approaches I think which will help uh uncover some just some terrific ideas that we can chase down and hopefully cure more cancers looks like you agree with that Dr dies I certainly do yes I think the the next Frontier for us and something that we're actively working on are vaccines targeting cancer risk factors like chronic inflammation um so vaccines to prevent fatty liver disease or we're working on a vaccine we call advac which is directed against um obese adipocytes so this would potentially while people are trying trying to um change their lifestyle be able to reduce their risk of the development of cancer by controlling that chronic inflammation at the tissue level fascinating you know this discussion has been eye openening I thank you all for joining us and I thank you for your work too thank you so very much it was great talking with you great talking with you yeah the same thank you for having us tomorrow's cure is a co-production of Mayo Clinic and PRX our senior producer is Nancy Rosen Bal our theme was composed and produced by Terrence Bernardo and the show is mixed by Tommy bazarian we had research and production support from David Newtown Deborah Bazar and Jenna viiv sponsler Tony Carlson is our production manager and our executive producer is Joselyn Gonzalez be sure to follow tomorrow's cure on iHeart Spotify or wherever you get your podcasts I'm your host Kathy wer thanks for listening