A Gateway to Empowerment: What to Know About Molecular Imaging

[00:00:00] Adam Walker: G. E. Healthcare. G. E. H. C. is a leading global medical technology and pharmaceutical diagnostics innovator. G. E. Healthcare is deeply committed to ensuring that the MBC community gains greater familiarity with the expanding and critical role of molecular imaging patient care and that people living with NBC and their loved ones have access to the tools that physicians rely on when developing treatment.

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.

Molecular imaging tests can offer comprehensive views of breast cancers, especially for locally advanced or metastatic breast cancer, and can help paint a clearer picture of the extent and characteristics of the cancer. This can give doctors the ability to help guide treatment and evaluate response to treatment.

Joining us on today’s show is Dr. David Mankoff, Vice Chair of Research Radiology and the Matthew J. Wilson professor of radiology at the University of Pennsylvania and the Associate Director of Education and Training at Penn Abramson Cancer Center. Dr Mankoff is going to help us understand the complexities of breast cancer tumors what these molecular imaging tests are looking for and who should be getting them.

Dr. Mankoff. Welcome to the show!

[00:01:19] Dr David Mankoff: Thank you very much for having me. It’s a pleasure to be here.

[00:01:22] Adam Walker: I appreciate you taking the time to do this. I think these tests can be confusing and I’m hoping to be less confused at the end of this conversation. So thanks for doing this.

[00:01:34] Dr David Mankoff: I am hoping you’re also less confused. Yes, I have no doubt. I have no doubt your listeners are less confused afterwards, too.

[00:01:41] Adam Walker: That’s it. That is ultimately the goal. So can you explain what a breast cancer biomarker is? Why it’s so important for both patient and medical team to know and understand their tumor characteristics when things are diagnosed?

[00:01:54] Dr David Mankoff: Yeah, it’s a good question. And a biomarker is a general term that is used to tell you something about, in this case, an individual breast cancer and the individual that carries that cancer with the hope of

developing much more individualized treatment. So for example, a biomarker might tell you, what are the features of that tumor that might lend themselves to certain forms of treatment? How likely is it that this tumor is going to be aggressive and I need to act quickly versus more indolent? A biomarker can also be a response biomarker so that when you’ve given a particular treatment, a drug, for example, you can tell whether or not it’s working. So in general, biomarkers are the tools that we use to be able to guide individualized, pre treatment for each of our patients.

And we sometimes call that precision oncology. An example for the listeners that they might understand is that it may be used to, thinking about the estrogen receptor or as part of one of the tests that are applied to a breast; biopsy or breast tumor surgical material.

And that really helps guide exactly how to treat that particular type of tumor, including choices of therapy, such as an aromatase inhibitor or tamoxifen.

[00:03:10] Adam Walker: Got you. I appreciate that description of biomarkers and helping direct personalized treatment. That’s really helpful. So I understand that breast cancer tumors can change and evolve from the initial diagnosis when a patient’s diagnosed with a metastatic disease.

Does that mean recurrences can be different from the original breast cancer? And can you have two different types of cancer in the body?

[00:03:32] Dr David Mankoff: Yeah, that’s an excellent question. So let’s start with the simplest case where a patient is presented with a tumor that may be in the breast or in the lymph nodes.

And where that tumor to recur or come back, it could come back and spread to our other parts of the body. Tumors by their nature are somewhat genetically unstable, and so they have mutations and they tend to evolve much as people and animals and plants would evolve in the wild, but a much faster rate.

And so at each one of these steps, there can be features that change in the tumor over time, and there may even be different sites of disease that have different characteristics in somebody who has spread to multiple parts of the body. And in particular, that’s a topic that is an area that I focused on as a molecular imager, because where we traditionally rely on a piece of tissue to get these biomarkers and understand what the tumor is made of and how it’s likely to behave and respond to therapy; when we have widespread cancer that’s in more than one spot, in metastatic breast cancer, for example, we take a biopsy of a site that’s accessible and convenient, but there’s no guarantee that the disease is

uniform across the other sites of disease because things may have evolved over time or as a function of location. So the concept of molecular imaging is to give you some of the information that you get from a biopsy about tumor features beyond just detecting the tumor and in particular to be able to look at those features across the full burden of the disease, not just happen to be the one site where you put your biopsy needle on to get a sample.

[00:05:15] Adam Walker: Okay. Got you. So, let’s talk about imaging. You mentioned imaging, so far. So talk to me about the imaging tests that are used to evaluate breast cancer progression and how these tests inform treatment plans and particularly with patients with MBC.

[00:05:32] Dr David Mankoff: Yes. And so I think when people think about imaging tests, they’re probably most familiar with the tests that are used to detect and diagnose breast cancer.

Something like mammography, or these days, tomosynthesis, an ultrasound, breast MRI, for example. Those are all scans that will show structural features or composition of the tissue and in general we recognize tumors as something that looks structurally and anatomically different than what we see in the normal tissue in the breast.

We’re looking in the liver for spread, compared to the normal liver. So this same principle is used not only to help people diagnose breast cancer to look for abnormal structure. That same principle has been traditionally used over time to look for evidence of tumor spread. For example, a CT scan, a CAT scan is an important part of staging or determining the extent of disease.

And so it is pretty widely available, very fast and widely used. And so it is a way to recognize tumors because there’s an abnormal structure in the breast or a certain part of the body, based upon those features. My area of research and what we’ll spend most of the time talking today is called molecular imaging.

And in this situation, and it’s mostly the most commonly used molecular imaging modality right now, especially pet positron emission tomography. In this situation, we are able to use contrast materials to help us find these tumors that are actually molecules that are designed to tell us something about the tumors we’re looking at.

And for example, the most commonly used form of that is a glucose analog. Those tumors that are more aggressive will tend to use at a higher rate. And that allows us to not only detect them, but to identify how aggressive they are, and

also to assess their response to therapy, where we can see some decreases in their ability to consume glucose as we start to treat them effectively.

These are highly complementary to anatomic imaging, in that they tell us something about biochemistry and the biology of the tumor. And these days, when we use a PET scan, for example, we usually combine it with a CT so we get molecular information, combined with anatomically. That’s a lot of words and a big concept to swallow, but this brings a new way of looking at tumors that not only finds them on the basis of their structural and anatomic abnormalities, but helps define and to define them on the basis of their molecular features.

Much as one might start to think about happens in pathology. A very concrete area of that’s relatively recently been FDA approved, is the ability to identify whether a tumor site expresses the estrogen receptor that we talked about before. And this is a technique using a probe called Fluoroestradiol, it’s called Seriana commercially, and it is basically a close analog of estrogen and binds to the estrogen receptors, which is what their function is, and can image the presence or absence of these receptors in the entirety of the body.

So if somebody had an ER expressing tumor, an ER positive tumor, that, somehow, because of changes in genomics or other features of the tumor, lost that estrogen receptor on the way to becoming a metastasis. That would be very hard to identify with a biopsy, because you’d have to biopsy every side of the tumor. But something where imaging is ideally suited. And so it’s one of the more recent additions to this armamentarian that begins to see how imaging can play a role working with biopsy and pathology to help guide treatment and guide precision in individualized treatment.

[00:09:22] Adam Walker: Alright, so I’m curious to compare imaging and biopsy results.

Like what additional information can we get from molecular imaging that biopsy results might not tell us?

[00:09:34] Dr David Mankoff: Yeah. Let me, turn that around and say, what can you get from a piece of tissue that’s hard to do by imaging? When you get a piece of tissue, you can do assays for many different properties. Estrogen receptor, the rate at which it’s growing, genomics. And so you can get a lot of depth from one part of the body. Molecular imaging, on the other hand, might tell you one or two features, maybe a few more about that tumor. And so it doesn’t have the sort of depth of information that you would have with a biopsy, but it can image every site in the body.

So especially in more advanced tumors, locally advanced breast cancer that’s in the breast and the lymph nodes or metastatic breast cancer that spread to other parts of the body. This was one of the few ways of identifying and understanding what’s happening from a molecular biochemical standpoint at each site.

So you can look at the heterogeneity of these tumors. We talked about the fact that the tumors can be different from site to site or heterogeneous. You can look at the way individual tumors respond biochemically, which gives you a very early indication of response. You’re giving a drug, does it work well for the liver but not the bones, for example?

That’s very hard to tell from other forms of imaging. This imaging can give you some early indications of how that’s working across the full burden of disease. So the big difference is, learning a few things about the entirety of the body, burden of disease, learning a lot of things from one particular area that you sample.

Now maybe you sampled the piece of the tumor that is the less likely to cause problem for that patient. Then you may have missed the problem child if you want to think about it, and that’s right.

[00:11:14] Adam Walker: Interesting. All right. So let’s talk about, when people need imaging, let’s talk about self advocacy for a minute.

So I guess my first question is, are these tests readily offered to patients? And if not, should patients be considering them, should they be asking for them? And how do you know if a molecular imaging is a test they should be asking for?

[00:11:36] Dr David Mankoff: These are very good questions. This is probably best worked out for the most commonly used PET scan, which is the glucose PET scan or fluorodeoxyglucose, called FDG PET. That’s actually been implied fairly widely, the breast cancer, and there’s a fair amount of data on where it can be helpful. And so sometimes patients will come into the office saying, “I’ve heard of this really cool thing towards the PET scan. I want one.” But for example, if you have a very early tumor that hasn’t apparently spread to other sites of the body and doesn’t have other aggressive features, it probably doesn’t make sense to start with a PET scan because you’re going to find the tumor you already found. And none of these tests are perfect.

So you may find something that is a false positive that uses glucose because of inflammation or injury or some other process. So patients should be aware of the technology that’s out there and can advocate for themselves. But, it’s also

very important for the folks that are caring for them understanding and know these guidelines, which are now actually published in the National Comprehensive Cancer Network Guidelines.

And so most well trained and practiced breast cancer specialists, oncologists, people working in the area, I have an idea of how to apply these tests.

[00:12:54] Adam Walker: So you mentioned people coming in, having heard about a test, asking for a test. And I often imagine patients advocating for themselves related to drugs, “oh, I heard about this drug. I’d like to check that out.” I don’t really think about it in terms of scans. So I guess my question to you is, are we getting to a point where patients feel more comfortable asking for different types of tests, different types of scans, in the same way that they do for different drugs?

[00:13:19] Dr David Mankoff: Yes, I think people are starting to have more information and be good consumers, and be able to advocate for themselves. The other thing is, some of these tests are getting a little bit more expensive than some of the other tests, so we don’t necessarily use them on everybody. And sometimes insurance agencies will give us a hard time in supporting them, despite them being on the guidelines. So this is an opportunity like a drug where a patient can be an advocate and working with her oncologist or a surgeon or radiation oncologist, to do that. But, as a nuclear medicine specialist, I will occasionally be one of the people someone will see for treatment, not so much for breast cancer, but for other diseases that we treat with isotopes such as thyroid cancer.

And I’ve had patients walk into my office and say, I “want a PET scan.” Sometimes that’s correct. And that’s what I do for a living. So you would think I would want everybody to get a PET scan, but there are nuances. One of the areas of research that I contributed to is when these PET scans were first brought about, everybody said, “Hey, I want something that looks at my whole body, and it’s very sensitive pet scan that can tell me everywhere my disease is.”

And then, lo and behold, some studies came out that with people with very early breast cancer, and a very low risk of spread to other sites of disease, in these tests that are good, but not perfect, there were quite a bit more false positives, red herrings that showed up on the scan than true positives.

And so the guidelines came out that really you want to have the following features of presentation, a more aggressive tumor, some obvious spread to lymph nodes or some concern about spread to the other body so that your pretest likelihood is high enough to justify the scan and to be able to interpret

the results in a way that benefits the patient, rather than just delays care because of these false positives.

That’s a really difficult conversation. I’ve had to have that conversation myself as the pseudo oncologist treating somebody with radio isotopes and people walk in the door and they say, “I want the fanciest diagnostics that I can have. I want these tests from my blood. I want these tests in my tumor. I want these, scans.”

And I say, ‘I don’t think that’s appropriate.” And they go, “why not? It’s just diagnostic.” But if you use diagnostic tests inappropriately, you can get misleading information no matter how good the tests are.

[00:15:33] Adam Walker: Yeah. I never would have thought about the false positive angle of that, but that makes so much sense and it seems like it could be a huge risk because if you go really far down the wrong path, that’s bad.

[00:15:46] Dr David Mankoff: It is, there’s an old saying, if you go to a surgeon and ask about surgery, you’re going to get surgery. if you go to a radiologist and ask if you need a scan, they’re going to say yes. And I think it’s been very important that both surgeons and radiologists and a bunch of other people working in the field will occasionally answer no and say here’s why not.

And these diagnostic components can be very hard to understand. They don’t have any apparent downside other than their cost, but in many cases I’m finding the appropriate test to be used in the appropriate setting. For example, in the estrogen receptor agent that I talked about that’s new, and I think a number of people who will be listening to this have probably heard about it, again probably doesn’t make sense to take a very early tumor where you can biopsy it and find the estrogen receptor and use this.

Advanced test to do that. On the other hand, somebody who may have had an estrogen receptor positive tumor may have broken through some treatments, like an aromatase inhibitor or tamoxifen that are designed for that. That may be an appropriate test to try to identify which of the tumor sites do or don’t still retain the estrogen.

But it wouldn’t make a whole lot of sense and probably not be useful and helpful in very early stage disease and patients that haven’t been treated.

[00:16:59] Adam Walker: Okay. So, let’s talk about the myths for a minute. What are some of the myths that you hear about molecular imaging? And one that I’ve heard before is, concerns about radiation exposure, for example.

So tell me about that. Are the tests safe? What are the myths?

[00:17:15] Dr David Mankoff: Yeah. And to amplify on the fears, what we do in nuclear medicine is in general, including PET is we use radioisotopes. And when we do diagnostic scans, we inject, typically in a vein, a radioactive tracer, and then use detectors to find that.

People think, “wow, they’re injecting me with radioactivity, that sounds creepy,” and shouldn’t they be doing that to me? But in general, these are very short lived isotopes. They’re very low dose. And in many cases, the actual radiation does due to the radioactivity exposure for a diagnostic scan can actually be less than what you would get for a cat scan, for example.

So these are yes, an unusual way of doing this study. But the relatively low radiation, I would imagine most breast cancer patients who have had slightly more advanced cancer may have gotten the bone scan in their lives. And the bone scan is exactly the same idea. You get injected with the radioactivity, 2 to 3 hours later, you get a picture of the bones and it tells you whether there’s anything that looks like spread to the bones.

So we’ve been doing this for years and years. We don’t use these radiation generating tests where we don’t need to. That goes back to my prior conversation. But in terms of the risk of these studies and the amount of radiation they’re getting, the risk of any radiation coming from diagnostic radiology pales in comparison to very appropriate risks that come with. And if you can say, “look, giving using the imaging test to give you the right treatment, minimizes the risks of that treatment quite a bit.”

Then the risk of the radiation exposure, which is quite low is really infinitesimal. The risk benefit ratio is strong. It falls on part, appropriate choice for testing. So people shouldn’t be scared of it just because it’s something they hadn’t heard before and they have to get injected of this.

Creepy stuff. And isn’t that how Spider Man turned into Spider Man from Peter Parker? None of those things come back. When we give people isotopes for therapy, the first thing I tell them, I go is, “you’re not going to start shooting webs or being able to jump all the tall buildings. I’m sorry. Otherwise we get a lot more people coming.”

[00:19:23] Adam Walker: Just tell them there’s no radioactive spiders involved and then they’ll be like, “ah, okay, I got that. I got that.” So all right.

[00:19:31] Dr David Mankoff: We don’t glow in the dark, unfortunately. That’s great.

[00:19:34] Adam Walker: These advances are amazing Dr. David Mankoff, I really appreciate you taking the time to share them with us today and just helping to educate me and our listeners on just all these new advances.

Where can our listeners go to find more information about these types of tests?

[00:19:52] Dr David Mankoff: So there’s a few resources. There’s a fair amount of information that is associated just by going out to some of the suppliers of the what we call the radio pharmaceuticals, the tracers, the equipment that’s done.

There’s a number of organizations. There’s some material that we’re beginning to put together, including these podcasts through Komen that go to a very general audience. I’m involved in an organization in the Society of Nuclear Medicine and Molecular Imaging, the SNMMI, and there’s an outreach group there that provides both outreach to physicians, so they can be trained in some of the things we talked about before, but has a patient outreach group and has developed a fair amount of material on that.

I think most of that is available through the Society of Nuclear Medicine and Molecular Imaging, website and be happy to send you some contacts and pointers in that regard. You’ll also find some of these in less specialized radiology channels. For example, the American College of Radiology, the Radiologic Society of North American will also have links to these different tests and help, them.

There’s actually some material that’s just in the sort of material available on the web. That’s not bad, but there’s also a fair amount of misinformation in some of those sources. And so I would encourage listeners to go through Komen, trusted partner, or through one of these societies that have outreach components to get the latest and up to date, information.

[00:21:15] Adam Walker: Dr. Mankoff, so great to talk to you. Really appreciate you joining us on the show today.

[00:21:20] Dr David Mankoff: It’s my pleasure. I want to thank you and the Komen organization. They’ve really done a lot to both advance science and to help patients and I’m very pleased, proud and thankful to be part of it.

[00:21:32] Adam Walker: GE HealthCare is a leading global medical technology, pharmaceutical diagnostics, and digital solutions innovator, dedicated to make clinicians more effective, therapies more precise, and patients happier and healthier. Serving patients and providers for more than a hundred years, GE HealthCare is advancing connected and compassionate care, while simplifying the patient’s journey across the care pathway. Together we’re creating a world where healthcare has no limits.

Thanks for listening to Real Pink, A weekly podcast by Susan G Komen. For more episodes, visit realpink.komen.org. And for more on breast cancer, visit komen.org. Make sure to check out @SusanGKomen on social media. I’m your host, Adam. You can find me on Twitter @AJWalker or on my blog, adamjwalker.com.