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Precision Medicine for Breast Cancer

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Published on March 16, 2020

Key Takeaways

  • As cancer treatment is more and more precise, genomic profiling tests are important for every patient.
  • There are new HER2+ drugs like tucatinib having success in clinical trials.
  • Everyone can have access to the most up-to-date treatments, they just need to make sure their doctor is communicating with other experts.

The future of breast cancer treatment is in a more precise, individualized approach with better outcomes and fewer side effects. As leading expert Dr. Vijayakrishna K. (V.K.) Gadi says, “Precision medicine is about giving the right medicine to the right patient at the right time.”

Tune in to hear Dr. Gadi explain how doctors are using specific tests to paint a “molecular portrait” of a person’s cancer to identify which patients will benefit from which therapies—and his advice for patients in rural areas to gain access to the latest treatments.

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Transcript | Precision Medicine for Breast Cancer

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrea Hutton:            

Hello, I’m Andrea Hutton from Patient Power, and I’m very excited to be here today at the San Antonio Breast Cancer Symposium. The largest breast cancer conference in the world with Dr. V.K. Gadi, who is an Associate Professor and Medical Oncologist, and very excited to talk to you today.

Dr. Gadi:                

I’m glad to be here.

Andrea Hutton:            

And, what I want to ask you about is precision medicine in breast cancer. So, I’ve heard these terms. What does that mean for patients? Tell me what it is.

Dr. Gadi:                

I like to distill it down to the core of the words, which is it’s the right treatments for the right patients at the right time, right? And, that can mean a lot of different things. Because if you take a very precise medicine that only hits one thing inside a cancer cell, but that thing’s not important for the next patient, that’s not so precise, right? So, there’s a lot that goes into it and the first question is: Is this the right patient for this precision approach, whatever that might be? 

And, if—for example—if it’s an early stage breast cancer, we can take very imprecise ways of dealing with that early stage breast cancer, but that’s not going to help the patient. So, that might be too many treatments, too many things that aren’t needed for this little tiny breast cancer. On the other end, if you have a very precise approach but it’s a big problem, like a big cancer that needs lots of modalities to take care of it, then it doesn’t matter how precise that approach is. It’s not the right one for that patient. So, the first thing I take when I look at this problem is, I step back and say, “What’s the patient needing?” Right? 

So, then the next level of what precision can be is very different depending on the specialty of the type of doctor. You can have precision approaches with radiation therapy and with surgery. I’m a medical oncologist, so I’ll just focus on that today. In terms of the latest and greatest in precision medicine, I think about it as two phases. There’s what we do with patients and working with patients with early stage breast cancer, and then there’s how can we be more precise with patients who are dealing with advanced or metastatic cancer? 

I think the biggest things that have happened recently in our field with that early space is we’re finally recognizing that not all our patients need all the therapies we have. And, we’ve been in this paradigm where we’ve just built on all these treatments we’ve had and just layered them on and layering on toxicities at the same time. And, when you do too much for somebody who doesn’t need that much, all you’re doing is not helping them live longer. You’re just helping them live with more toxicities, right? And, that’s not fair.

So, some of the coolest things that have happened are these gene expression tests, and those are truly precision medicine. We can take a cancer specimen from a patient, we can look at a specific type of genetic material from that cancer, and look at how the genes are turned on and off. And, basically, make a molecular portrait of that cancer and that portrait is for that patient, but the thing that’s cool about it is those same portraits, we can then match up with other women who’ve also had that test on these trials and whatnot. The only difference there is we know what happened to them based on their choices.

So, in a typical one of these types of gene expression tests, you might be able to say, “Hey, you’re high-risk. That means if all we do is anti-estrogen treatment for you, that’s not enough. We also need to do chemotherapy.” And, guess what? If you get chemotherapy, your outcomes actually look kind of like the people that had the low-risk cancers in the first place. And, on the other end of the spectrum, we might be able to say, “Hey, this is a low-risk situation, and this test tells us the same thing. Congratulations. You’re not one of those patients that needs chemotherapy and all the other tough medicines we have. Here’s a pill that takes care of the estrogen in your body and that’s going to help you the most.”

And, so, that’s a precision medicine approach, and I don’t know that a lot of people think about it that way. And, certainly, it wouldn’t be appropriate to use that precision test on somebody who might have advanced cancer, right? Because they have different needs. So, those are some of the exciting things I think are going on in precision medicine in early stage breast cancer.

Andrea Hutton:            

Now, is that the Oncotype test? Or the MammaPrint test, or are those the things that…

Dr. Gadi:                

…Oncotype, MammaPrint, Biotheranostics, Prosigna—there are a number of tests available and I think what we’ll need to do is fare it out. Which one of these is the best for the particular situation. There’s a lot of debate, even at this meeting, about what these different tests can tell us and how they’re being used. So, I’m trying to stay, for the most part, agnostic of the platform and respect that there might be different types of knowledge gained from the different tests. 

Andrea Hutton:            

That’s something as a patient my doctor orders, I get a score, they interpret that score, and they say, “Chemo or no chemo,” essentially?

Dr. Gadi:                

Correct. That’s what it boils down to a patient, yeah. But, I think, again, I’ve seen it too many times where physician well-meaning enough is ordering the wrong test on the wrong patient, and then you can’t make those conclusions, right? So, it really matters—us understanding how to be precise with certain patients. Some of the data right now, for example, in patients who have many lymph nodes involved—these tests don’t have a role in those patients’ care yet. We’re hopeful, but they’re not there yet.

Andrea Hutton:            

And, so, for the later stage patients, what is precision medicine mean in that circumstance?

Dr. Gadi:                

So, here we’re not only looking at precision approaches to identifying which patients would benefit from which therapies, but the medicines themselves have become more precise. So, most of the treatments we use are blunt force treatments. They, on general principles, take care of some big aspect of a cancer and try to get after it that way. So, simply put, chemotherapy is a very dumb medicine. It just simply kills anything that tries to divide.

Andrea Hutton:            

Including my hair and my skin?

Dr. Gadi:                

Correct, and your bone marrow, and all these places, right? That’s very imprecise medicine. It’s effective, but it’s very imprecise. When I think about the medicines themselves being precise, it’s specific molecular pathways in the cancer that are promoting the cancer’s growth, and if we can just stick a little pin in one of those and block it, then maybe the cancer falls apart. And, this meeting has been an excellent example of some of those precision medicines kind of getting to the forefront.

I’ll just call one out in particular. There’s a molecule called tucatinib at this meeting that was discussed a lot. It’s a specific inhibitor of mutations and the HER2 pathway. If that’s activated in a cancer, it’s a powerful gift for the cancer, because it really helps it grow fast, but you block this little pathway in there with this very precise medicine, and all of a sudden the cancer can’t grow. And, we saw at this meeting that that medicine not only does that very effectively, it does so—generally speaking—without a whole lot of additional toxic side effects that other pathways that it’s incidentally blocking. So, that’s an example of a very precise medicine. 

There are also some posters, as well as session talks here this weekend, where they’ve looked at precision tests in those same metastatic cancer patients. One comes to mind where people are now testing the blood to look for specific mutations that are arising in the cancer, and then once they’ve arisen, maybe we should go match that specific mutation to some new drug that we haven’t yet had our hands on reliably, but here we go. We put them together, and all of a sudden, the outcomes are better for that patient—all from a blood test. 

Andrea Hutton:            

So, that’s a liquid biopsy, right?

Dr. Gadi:                

A liquid…

Andrea Hutton:            

…when I hear “liquid biopsy,” I should think “blood test”? 

Dr. Gadi:                

Yeah, you should think blood test. So, in this particular case, they were looking at genetic signatures that the cancer was releasing into the bloodstream that you could pick up in the serum just from a simple blood test. There are different definitions of liquid biopsies, but this is what this was in this case.

Andrea Hutton:            

So, does that mean I don’t have to get a biopsy of a tumor? Not yet? 

Dr. Gadi:                

It’s a little early for that because there are still lots to learn from the biopsy of the tumor. You know the phrase: “A picture is a thousand words”? When you look at a cancer underneath the microscope, you not only see the cancer cells, you see all the neighborhood things that are going on, and that can be very informative. Whereas when we’re just doing the sampling in the blood, it’s a very small sense of what that cancer’s doing. So, for the time being, I think we need it all. But, it’d be nice to be able to say to a patient, even farther down the stream, “Here’s my iPhone, and I figured out you have some cancer,” right? So, that would be really tremendous as well, but we’re not there yet.

Andrea Hutton:            

Not there yet? Okay. We can always hope. 

Dr. Gadi:                

Yes, I’m working on it. 

Andrea Hutton:            

Okay. So, we have precision for certain kinds of advanced breast cancers?

Dr. Gadi:                

Mm-hmm. 

Andrea Hutton:            

Is that endless? Are there endless targets? Are there endless medicines? 

Dr. Gadi:                

It feels like it could be endless. It is really a finite number of things, but the number of ways a cancer can be different from one patient to the next is innumerable. And, that’s going, again, looking at how can we be precise with the patient, right? It’s not just, “You have mutation in this one gene,” but, “You also have these other things that are going on.” 

And, integrating all of that—it takes a lot of kind of computational power, brain power, to kind of figure all of that out. But, it’s unfortunately not that simple. I think we’ll have a finite number of tools, i.e. drugs, that we can use, but putting them together in the right combinations to figure out what’s right for a patient is the next challenge we’re going to be facing. 

Andrea Hutton:            

One of the things I wonder about that’s coming in the future that I hear about is that we will stop maybe thinking about cancer in terms of where it arises. It’s not going to be breast cancer and lung cancer, it’s going to just be the characteristics of my tumor. So, are we there yet? What’s hap…?

Dr. Gadi:                

…we’re getting there. So, what I’ll say is that in the context of an early stage cancer, whether it be lung, breast, colon; those are cured of cancers. Those are cancers that we’re now approaching with, “This is something we hope never comes back.” And, we’ve worked very hard to put all these modalities together, whether it be surgery or drugs and radiation to achieve that cure. I think that’s still going to be the paradigms for those early stage presentations, but in the metastatic setting, you see this convergence of mutations and things that are shared between different kinds of cancers. Depending on where they might’ve started kind of doesn’t matter anymore.

So, I have—for example—in the last few years, there’s this movement where you’re seeing drugs being FDA-approved not for a specific cancer, but for a specific set of cancers that have a common theme with them. I’ll highlight. For example, there’s an immunotherapy called pembrolizumab (Keytruda), and it actually has an FDA approval that’s agnostic of where the cancer started, but the key feature is that it shares something called microsatellite instability. If you have that feature, this is a drug you can use, and you’re going to see more of that.

There’s a drug called neratinib (Nerlynx), and tucatinib, and others like it—for example—that target HER2, this growth signal we were talking about a moment ago, that is really important in a lot of breast cancers; but it turns out it’s important in five percent of lung cancers, five percent of colon cancers, 10 percent of bladder cancers. So, why would we just only approve it for breast cancer when there’s a real chance it could work for these others? 

Some of it is hard, because we have built up a system for regulatory kind of oversight and how we do drug development that thinks about these diseases based on where they started. And, it takes a little bit of reset and some courage to say, “Okay, let’s blow up what we have and see if we can just acknowledge that these are cancers that share the same things, and then maybe develop drugs based on that feature.”

Andrea Hutton:            

So, I’ve also heard about people whose doctors have sent their tumors out, and they come back with a report that says, “Oh, you have these targets, these mutations and there are these 25 drugs that might work.” 

Dr. Gadi:                

Yeah. So, I’ll tell you what these are. There are a variety of things being done, and just in the fullness of disclosure, I’ve been very involved with this, and I’ve actually personally launched a company that does this kind of thing. But, essentially, most of the testing to date is just looking at DNA or RNA, nuclear material from the cancer cell, to understand what it’s doing. 

But, the way I think about that is having a two-dimensional map and trying to navigate your city with an unfolded map and kind of saying, “I think I’m supposed to take a right here,” but who gets around anywhere like that now? Basically, you pull up your iPhone, you type in an address, and it tells you where to take a right turn, that there’s a traffic block—it’s functional. It’s a functional map. 

So, the next phase of what we’re doing with precision medicine is functionalizing that genome. And, for example, we can now regularly take cancer cells from a patient, grow them as these things that we call organoids—so, these are miniature representations of the cancer grown out of your body. And then using very complex sort of algorithms, treat those miniature cancers with a variety of drugs and combinations, and then come back to a patient and say, “Hey, based on what this cancer is and what the mutations are—and by the way—how these drugs kill the cancer, this is your best choice.”

And, so, we’re there now. There are many clinical trials that are being started where they’re going to functionalize the genome to make the best choices for a patient in that patient. 

Andrea Hutton:            

But, that’s very individualized. That is literally… 

Dr. Gadi:                

Highly individualized, yes.

Andrea Hutton:            

…the definition of precision is “me.” That literal…

Dr. Gadi:                

…correct, correct. Because that report is not transposable to the next patient, because that report is based on what came out of your body, yeah. 

Andrea Hutton:            

Well, that kind of seems like sci-fi, and yet…

Dr. Gadi:                

But, it’s happening now.

Andrea Hutton:            

…it’s right here now, yeah. 

Dr. Gadi:                

Yes, yes. There’s commercial companies doing this. 

Andrea Hutton:            

And, so, the community oncologist in a small town who doesn’t have the same kind of access as somebody else in a research hospital or a varsity, isn’t probably going to have access to these things quite yet. And, the insurance companies maybe aren’t catching up…

Dr. Gadi:                

Right, yeah.

Andrea Hutton:            

…quite yet as well. So, as far as what’s really here right now for precision, how precise are we today? 

Dr. Gadi:                

So, I have this lovely quote that I have from a colleague of mine that I work with, which is: “Your ZIP code should not dictate your cancer care.” And, I firmly believe that. Access is key. As fancy as our medicines are, if we’re not getting them to the patients that actually need them, it’s a true failure of the system. So, there’s a lot of messaging, there’s a lot of negotiating with insurance companies, and there’s a lot of network building that needs to take place.

I shudder to think that I could go out into the community and practice lung cancer. I’m so far removed from that in my career. At this point, I’m a breast cancer expert, and very narrowly at that. So, it’s not a judgment on what people are doing elsewhere. It’s an opportunity for collaboration. Hopefully we can cinch up all those loose ends and get people in so that they can get their information from a set of academic experts on a very complicated cancer, deliver that information to that patient wherever she or he might be, and then have that plan be put in place by the local oncologist.

And, that’s my vision for that. We’ll see how much work it takes to get there, but I think there are a lot of people talking about this, and it may be the next phase of oncology innovation. It’s not something with new technology. It’s how do you actually get a drug to a patient who doesn’t have all the resources that somebody in a city might have?

Andrea Hutton:            

And, if there’s one thing that you can tell a patient who doesn’t have the opportunity to see you, but who is watching this online, who doesn’t live in a major… 

Dr. Gadi:                

City. 

Andrea Hutton:            

…city, what is the best thing that they can—how can they address this question with their doctor? What are the best questions to ask?

Dr. Gadi:                

So, oncologists are pretty tied together, even those in rural areas, and it just sometimes is a matter of making a phone call and running a case by an expert, so to speak, and then getting some input that way. So, I recognize not every patient’s going to be able to travel to a major place. Sometimes even the bus fare for somebody who lives in the inner city trying to get to a cancer center is a challenge. 

So, wherever the patient is, we need to figure out what technologic solutions we have, virtual or otherwise, to get those answers to those patients. Whether it be wearables, teleconferencing, shared pathologists, whatever it is. We just need to figure that out. But, in an age when Amazon can deliver a package to me in the same day, I feel like we can get information back and forth between the community in rural areas as well.

Andrea Hutton:            

Well, thank you for taking the time to talk with us about the present and the future. 

Dr. Gadi:                

Sure.

Andrea Hutton:            

And, knowledge and hope go a long way for our patient communities.

Dr. Gadi:                

I agree. Thank you so much. 

Andrea Hutton:            

Thank you.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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