[00:00:00] Adam Walker: In honor of national breast cancer awareness month. If you'd like to join the fight against breast cancer, please go to www.komen.org and donate today.
From Susan G Komen, this is Real Pink, a podcast exploring real stories, struggles, and triumphs related to breast cancer. We're taking the conversation from the doctor's office to your living room. Today, we're speaking with Dr. Neil Vasan, an assistant professor in the department of medicine, division of hematology, oncology.
At Columbia University Medial Center., Dr. Vasan is a physician scientist who studies, how proteins function in breast cancer cell signaling, and how treatments impact breast cancer cell signaling, which is the communication within a cell. His research has been published in top scientific journals, including Science, Nature Cancer, Cancer Cell,
and Cancer Discovery. And he's received multiple awards, including being selected as a next gen star of the American Association for Cancer Research. Today, we're going to be discussing exciting new developments in the treatment of triple negative breast cancer. Dr. Vasan welcome to the show! 
[00:01:18] Dr. Neil Vasan: Thank you. Thank you for having me.
[00:01:19] Adam Walker: Well, I love talking with, with doctors and researchers on this show, it just brings so much breadth and depth to what we're talking about and the topic of breast cancer. So, first, can you talk a little bit about your background and what is a physician scientist? 
[00:01:36] Dr. Neil Vasan: Yeah. So I am, um, my sort of training, my educational training is that I have, I have an MD and I also have a PhD.
Um, and that's really what a physician scientist is. It's uh, it's someone who, um, uh, has medical training and done. Uh, clinical work, seeing patients, but also has a footprint in, in the laboratory. Uh, and in that case, my laboratory is what we call a wet lab. Uh, what that means is that we do bench work, um, and scientific experiments, pipettes test tubes, everything you see in the movies.
Uh, and that's the type of science that we do. That's the nature of the work we do. So it's a really exciting space to be in because we get to, um, uh, do work that is. In an arena that is certainly interesting from a basic science point of view, but actually has the real capacity to help patients at the end of the day and in a very direct manner.
Um, whether that is informing a clinical trial or making a therapy work, trying to make a therapy work better. Um, and it's also amazing to see patients everyday in the clinic who, you know, might be the beneficiaries, hopefully of some of the discoveries that I, and many of us in a field, or maybe. 
Okay. 
[00:02:44] Adam Walker: Wow, that sounds fantastic.
And when you talked about pipettes and test tubes, it took me right back to a high school. So, uh, thank you for that then nostalgic memory. Uh, so, so we're, we're going to talk about triple negative breast cancer a bit today. What about triple negative breast cancer makes it difficult to treat. 
[00:03:04] Dr. Neil Vasan: Yeah, that's such a great question.
You know, um, I think that, and I, I am sure someone who is connected to Susan G Komen came up with this sort of aphorism, but. Describe triple negative breast cancer, as you know, it might, it may have even been cliff Dr. Cliff Hudis, who's the, you know, the president of ASCO, um, someone in our field has, has made this really, they made this comparison, you know, triple negative breast cancer is challenging because it's a misnomer, you know, just because you're not, if you're not from Chicago or New York or San Francisco, it doesn't mean that you're from Los Angeles.
So it's this idea that it's sort of a misnomer it's that you don't happen to express the three major markers that we. Think about in breast cancer that we know can drive breast cancer, which is the estrogen receptor progesterone receptor, and a gene called her too. So it's just the absence of that. And so I think that is what makes it so challenging.
Breast cancer is a common cancer. There are a lot of patients who have triple negative breast cancer and were discovering new things about this disease really every day. And I will say that, you know, the last. Really 12 months have been pretty, maybe let's say 18 months have been pretty incredible in this field because we've had multiple new drug approvals, either first-in-class drugs or drugs that were approved in the metastatic setting and then made it into the adjunct in the, in the curable setting or drugs that, um, we figured out how to we, as a field, figured out how to make work a little better in these patients, or figure out who are the right patients who really benefit from this drug.
So it's actually been a really remarkable, um, one to two years. 
[00:04:35] Adam Walker: So you mentioned, you know, you mentioned drug advancements in the field. Are there any other advancements that you've seen in the clinic related to TMBC patients? 
[00:04:43] Dr. Neil Vasan: Yeah, you know, I think. Uh, change that is happening right now. Really a groundswell that's happening right now is the recognition that many of these patients can have genetic reasons that they have triple negative breast cancer.
So they get DNA from their parents. They could pass on these DNA, this DNA to their kids. So this is really important to know about. And. Up until very recently, we were using this knowledge to inform our treatment in patients with non-curable breast cancers, patients whose breast cancer has spread triple negative breast cancer that spread so called metastatic triple negative breast cancer.
But now we have data that if we give that drug in patients with curable breast cancer, who also happened to have these genetic mutations, it actually improves their, it improves the chance that, or it decreases the chance of the breast cancer will come back. And so. Is a treatment, but then also it's closely linked to a diagnostic.
And so we need to find out who are all these women with genetic predispositions to these cancers, because that can have tremendous impact, not only in the treatment that they're receiving and the, and the receipt of perhaps surgeries that could improve their outcome and, and decrease their chance of other cancers.
But it's also, there gets to be a real, um, You know, social and familial and even ethical issues and perhaps even dilemmas because. Obviously some of these patients you could imagine might be mothers with young children. How do we start to unpack that? And so, you know, I think most of us in the field are of the mindset, that data and knowledge is power.
And how do we, how do we use that knowledge and how do we deploy that to the best of our bills? Hmm. 
[00:06:23] Adam Walker: Okay. Wow. So, so let's, let's talk about, uh, about drugs for just a minute. You mentioned them earlier. I just want to go and ask you one of the more simplistic questions that I probably should know the answer to, but don't so what does it mean when a drug gets approved by the FDA?
[00:06:41] Dr. Neil Vasan: Yeah, that's, that's a great question. And, you know, I think that. Question is being experienced by the public really right now through all of the COVID vaccine work. Right. I think we're getting a, a firsthand glimpse really into this process, which of course has been under, uh, you know, has occurred for many decades.
But I think the public is really seeing what this means now and things like EUAs and acronyms like that, that were very much like, sort of legalees, uh, language are really now entering the common parlance, but. You know, I think it's important to note that, you know, every single drug that sort of goes up to bat, if you will, for FDA approval has already been vetted.
Tremendously over the course of many years, sometimes a decade in smaller, in, in, in, in stuck in many different types of studies. What can those studies look like? So some of those studies are studies done by people like me in the laboratory using proteins or using cells or using mice nonhuman. Those are what we call preclinical studies.
Sometimes those are referred to as phase zero studies. Then we do phase one studies, which are just questioning. Is this drug safe and tolerance? Um, is this drug or is this drug very toxic? That's usually a small number of patients that will get the drug. Uh, then we do, what's called phase two studies, which is saying, is there some efficacy?
Is there some hint of efficacy? Um, and then phase three drugs, which is really the pivotal sort of area is where we as a field ask the question, is this drug better than another drug? And that other drug could be what we call the standard of care, meaning. Treat these patients with normally this group of patients and most of the time that's another therapy, rarely that's actually what we call, you know, rarely, it's what we call best supportive care beating that unfortunately, there isn't much to offer these patients.
And so sometimes the comparitor arm or that what you're comparing it to is actually, um, uh, no active therapy, but nonetheless, um, that those phase three trials are really what, what comes out of that is really the, um, the sort of. You know, the wheat from the chaff, it's really the drugs that really, that make it for lack of a better word.
And then phase three trials. If they're positive, then they will generally go. You know, the, the, the groups of people that are involved in running the trials and the company that makes the drug we'll put together an application based on that huge amount of data that I just mentioned, um, that can span again, up to 10 years, put together an application for the FDA and.
As we've seen with the COVID backseat, that approval is actually multiple steps as well. Lots of different groups of people. It really is an apolitical process. I think that's really important to point out, you know, especially as many of the drugs that we use in, in cancer therapy today are really the result of, uh, a grief of collaborations between industry, which obviously is a business, right.
Academic institutions and individuals and patients, right. It's this sort of communication with everyone. And so I think it is important to note that that is the model that we approve drugs within the United States. Um, and so, you know, that's really the path for. Uh, for a drug to be FDA approved. And then when the drug is FDA approved, that's when you get, you know, you get a brand name.
Right. Which is usually some mumbo-jumbo, that's harder to pronounce. I don't know. I don't know who knows the answer to how to fix that problem, but that would be an interesting question. Um, you know, and then we, we also get a lot of data about safety, you know? Paul all these documents become very much publicly available safety documents, um, documents about, you know, in different populations is this struggle okay.
To give in someone who has kidney issues, as the struggle came to give it someone who has liver issues, can you give this drug in a woman who's pregnant, all these really real world, very important, um, cases that, that we have to try to understand. And I think that when drugs become FDA approved, I think it also gives the public sort of more.
Um, understanding of these diseases and disease subtypes. Um, for instance, you know, this is not a drug that's approved in metastatic triple negative breast cancer, but recently in the past two years, we've had the approval of a drug called a PI three kinase inhibitor in breast cancer. This is a drug class that I work a lot on in the lab.
And this is the first time in breast cancer where a mutation has sort of dictated the presence of a mutation in the cancer has dictated a you're a candidate for this therapy. Sort of which is a more of an abstract concept. Right? But that concept, I think became more clear for the public when they start to see, believe it or not advertisements or hearing doctors talk about this, these medications in the, in the lay press.
And it gives patients, I think the autonomy and the power and the agency to say, Hey, have I been tested for this? And so I think that that's how some of that information can sort of, um, diffuse into the public in a really positive. 
[00:11:35] Adam Walker: Okay. Wow. Uh, that was a great explanation 
[00:11:38] Dr. Neil Vasan: to answer your question from like a super, you know, legalistic point of view, but, uh, I think that's, I think that's really the fair, you know, the fair way to think about drug approvals.
And I will say that when a drug is FDA approved, that means it's, it's approved by insurance companies. So there's a whole set of, you know, very practical, uh, financial and legal implications from FTA. Wow. 
[00:12:02] Adam Walker: That's fantastic. I genuinely learned a lot in that. I really appreciate you sharing that. So, so related to FDA approval, why is it a big deal that, uh, is it Keytruda?
Is that how you pronounce that Keytruda was approved by the FDA for triple negative breast cancer? 
[00:12:17] Dr. Neil Vasan: Yeah. So, you know, this is a drug. So the Keytruda is the brand named pembrolizumab is the, is the generic name? I guess that's a rare example where the, I think the generic name is probably harder to pronounce,
uh, you know, these are so, so the premise of all of this work is that. Um, cancers can trick the human immune system and human immune system is what helps prevent against, you know, micro war, uh, viruses, bacteria COVID for instance, um, uh, and cancer has often figured out a way to trick the immune system to sort of cloak, uh, itself against the immune system and, and the work, the basic science work that led to these really fundamental discoveries resulted in Nobel prizes.
And this is really important. Uh, these are, these are tremendously important discoveries that have really changed the world. And so clinically, what that has resulted in is this really remarkable new types of drugs that are called antibodies. These are basically proteins that, um, hit a particular target.
Um, they're not chemotherapy. They have a very different, uh, side effect profile than chemotherapy. They don't cause hair loss for. Which is sort of the, one of the main side effects that people associate with chemotherapy. Um, and these drugs have really been remarkable in a large number of cancers, most notably melanoma or skin cancer, uh, kidney cancer, lung cancer, but.
And, and when that started happening, and I would say that those approvals happen to maybe six, seven years ago, something like that. So not, not that long ago. Of course the question was, well, do do these drugs work in breast cancer? And, you know, there were a lot of clinical trials that were done initially.
These so-called phase one trials, which I, which I referenced these small trials that actually showed that some patients did have a response, but it really wasn't clear who those patients were. Um, Sylvia Adams, Dr. Sylvia Adams, who's at NYU, did a lot of, some of the initial, really fundamental work in this field.
And then there were many, many large trials looking at other immunotherapy agents, not actually not Keytruda, but another drug called Atezolizmuab or to centric. And that drug basically the, um, Uh, and actually this, this harkens a little bit into that nitty gritty of what FDA approval means that drug receive what's called accelerated approval.
Um, and then the approval was contingent on a set of second trial to show that it confirmed what the first trial. So it turned out the second trial actually didn't show what the first trial showed. The first trial showed efficacy in, I'm not going to go into the statistics, but bottom line is it showed efficacy in patients expressing a certain marker in their tumor.
And actually didn't really show that in the second trial. So based on that, um, the company that makes the drug. Revoked the drug in a sense that's probably not the right word legalistically, but basically they're not moving forward with the approval, but what's, I think great for the field that happened in that moment in time, because obviously that's devastating for people on the drug.
It's devastating for the field. Is that Keytruda or pembrolizumab, those trials were reporting sort of at this time, it took about a year. Kept this all straightened out and Keytruda's, those trials ended up being positive in the metastatic setting, um, which was amazing and really, uh, wonderful for the field.
And now this is FDA approved. Um, there's some little intricacies that I'm happy to talk about, about the differences between these two drugs, but the bottom line is that it improves what we call overall survival. It improves survival. Bottom line, um, and improves survival by about seven months. Now that is not a long time.
And I think that just speaks to the challenges of treating this disease. It's a very recalcitrant disease. It's a very difficult disease to treat, but this is specifically in patients with a certain type of immune marker at high levels, um, who, who clearly benefit from this drug and this drug is given in combination with chemo.
So the other sort of piece of this that I would like to point out is. Many drugs that make it in the metastatic setting to get FDA approval. As, as we spoke about, are tested in the adjunct setting, which is that curative setting, patients who have curable breast cancers. And so. Drug in combination with chemotherapy also improves outcomes in patients with curable, triple negative breast cancers that also express these immune markers.
And so that data, those data sort of emerged at a similar time. Uh, we oncologists found out about that as a field, sort of at around the same time, which is interesting. I think that that gives a lot of safe, both for oncologists as well for patients that, okay, this is a drug that approved that, that works when the cancer spread, it also works when the cancer has not spread.
And so this means that this will be a drug. Many patients will receive, uh, with triple negative breast cancer. And of course it's our hope that patients who receive it when the cancer is curable, that fewer of them are going to have cancer that spreads and more of them will have their cancer cured. So that's really, you know, of course, It's been a really long winding road.
And you know, these drugs are now being looked at and other breast cancer, subtypes, ER, positive her two positive, but, and we'll see what those trials show, but certainly with triple negative breast cancer. We have a new drug, not a new drug necessarily, but a, a new approval. And this is really exciting for, for patients.
[00:17:29] Adam Walker: Well, it's exciting to see progress, right. And that's, that's really amazing, um, and appreciate the work that you do in those areas. So, so last question then, uh, from, from your unique perspective, what kind of treatments active or in clinical trials, are you excited about for patients? 
[00:17:47] Dr. Neil Vasan: Yeah, well, there's one other sort of treatment that, well, I guess two other treatments that are really important in this disease that are approved.
One is what's called PARP inhibitors. This is a class of drug that we specifically use in patients with BRCA mutations. So Brock has really one of the most common cancer genes that we know of. Again, uh, mutations that you, you, you might receive from your parents that are paths that you could pass down to your kids.
And we have drugs that specifically target. Uh, cancers, it turns out cancers that have those mutations are dependent on a certain repair pathway of DNA. Um, and, uh, we can target that repair pathway of DNA, um, using a drug called PARP inhibitor, these drugs, as I mentioned with Keytruda where it's approved in the metastatic setting and also in the curable setting.
So too, are these drugs they're approved in the metastatic setting and, um, uh, an approved now in. Curable setting. Um, there's another type of drug, which is called an antibody drug conjugate. And this is a drug called . This got approved in the last, um, one year, uh, I believe. And, um, uh, and this is a drug it's, it's a really interesting type of molecule.
It's basically an antibody. So, uh, like Keytruda in a sense, in terms of the actual business end of the molecule, the antibody linked to. Uh, chemotherapy. So it's sort of like a three in one little construct, and that is the active molecule and it hones in on breast cancer cells and then deposits the chemotherapy in the cells, sort of like a PE like a, like a smart bomb or like a payload, like that way.
Warren metaphor, but, uh, this drug is, uh, uh, F you know, it, it improves outcomes in metastatic, triple negative breast cancer. And there are many trials looking at it in the, in the curative setting as well. I think those are really the Mo I mean, those are all approved drugs. There, there are a lot of really interesting, and I think exciting drugs that are being looked at.
In, um, patients with metastatic triple negative breast cancer. And I think one big challenge, and this sort of gets to your initial question about what's so complicated about triple negative breast cancer is, um, we think a lot in medicine about biomarkers. We know that many drugs, if you just gave them to everyone with a particular disease, they, they may not work, but if you could figure out, okay, this group of patients, there's something about this group of patients where it works.
Oftentimes that's some sort of a molecular marker, a DNA mutation, something like that, that we can measure. Then if you give it to that group of patients, it may, it may work. And there often is a biological reason why that is. So how do we start to find out what these biomarkers are? And that's, that's one of the big challenges in.
I think medical science, um, and so many of the interesting drugs I think in this space are drugs that target specific biomarkers. So for instance, there's a drug that, um, called trastuzumab directs to can, or, and her too. So this is a drug that's now FDA approved in metastatic her two positive breast cancer.
Um, her two as a marker. When we call a cancer, her two positive, it has really, really high levels of her too, but her two can be in sort of low levels, but not zero. What we call her too low. Um, and. Currently the way we classify breast cancers, one little subgroup of patients with triple negative breast cancer.
I mentioned sort of that it's a misnomer, right? Um, one of those, you know, I, I made a city metaphor before. I'll just say like another city, if you will, is this her two low group? And so we actually have antibodies now that, that like, and her two that can target that for too low group. And some of those patients are going to be triple negative breast cancer patients.
So I think slowly we, as a field are starting to chip away at the. Complicated these complicated subgroups and come up with drugs that, you know, I think, I think, and I hope we'll be, we'll be effective, but we really need the support, you know, the continued support of Susan G Komen and, and of course the tremendous, um, you know, buy-in from patients and, and the, the willingness and the benevolence of patients to enroll on these trials and to, you know, um, hopefully be the beneficiaries of the drug.
Perhaps before it's FDA approved before it's sort of ready for the masses. Um, that's one upside that, you know, when I talk to patients about what are, you know, we all, we all know that there are a lot of, there can be a lot of that. There can be downsides to clinical trials, where there were risks to clinical trials.
And these are things that we articulate to all our patients, but there are benefits. And I think one benefit is, you know, it's sort of a. B being able to get a drug that could end up improving people's lives years before it's ready for the masses. And, and that's something that, um, you know, we don't know what that will be for a particular drug.
We don't know what will be a PR for a particular patient, but that's something that I want people to, you know, hang their hat on and, and have some hope in because that is a real. Benefit. Yeah. 
[00:22:36] Adam Walker: Yeah. Well, I, you know, I, I love conversations like this, uh, with, with researchers and, and physicians like yourself, it just gives me so much hope to see how far and how fast the medical community is just developing new treatments and new drugs and just new therapies.
Um, it's very, very encouraging, um, doctor Dr. Vasan. Thank you so much for your time with us. 
[00:22:58] Dr. Neil Vasan: Thank you so much for having me and thank you so much to Susan G Komen and to everyone listening 
[00:23:03] Adam Walker: in honor of national breast cancer awareness month. If you'd like to join the fight against breast cancer, please go to www.komen.org and donate today.
Thanks for listening to Real Pink, a weekly podcast by Susan G Komen for more episodes, visit Real Pink.com and.org for more on breast cancer. Visit komen.org. Make sure to check out at Susan G Komen on social media. I'm your host, Adam, you can find me on Twitter at AGA Walker or my blog, Adam J walker.com.