When it comes to cancer, there are many types of tests that can provide critical information–tests that can determine one’s risk of getting cancer, tests that screen for the presence of cancer, and tests that assess mutations or specific characteristics of a person’s cancer to inform treatment paths. Dr. Eric Klein, Distinguished Scientist at GRAIL, joins The Cancer SIGNAL to discuss the different types of cancer tests and each of their purposes.
Kim Thiboldeaux 00:09
Welcome to The Cancer SIGNAL, a new podcast presented by GRAIL, where we discuss the impact of early cancer detection, the science behind multi-cancer early detection and insight into how this approach has the potential to shift the cancer paradigm. I’m your host, Kim Thiboldeaux. We’re so pleased today to be joined by Dr. Eric Klein. Dr. Klein served as Emeritus Chairman of the Glickman Urological and Kidney Institute, Professor of Surgery at the Cleveland Clinic Lerner College of Medicine and as a member of the Department of Cancer Biology in the Lerner Research Institute. His clinical and research interests are in genitourinary cancers with special expertise in prostate cancer. He serves as editor in chief for UROLOGY, one of the four major urologic journals. He’s published more than 700 peer reviewed papers, including discovery papers that served as the basis for clinical assays for prostate cancer. Dr. Klein has extensive experience in clinical trial design and execution, cancer biomarker development, medical device development and employment, and healthcare leadership and management. He recently joined GRAIL as Distinguished Scientist. Welcome to the show, Dr. Klein.
Dr. Klein 01:17
Thanks Kim. Glad to be here.
Kim Thiboldeaux 01:18
So a lot to untangle here today, genetic testing, liquid biopsy, genomics, precision medicine, biomarker testing. We’ve probably heard at least some of these terms from our, our networks, our social media, or perhaps in the news. There’s more information available than ever before about one’s risk of developing cancer. In fact, our episode last month focused solely on just that, check it out, and what we can do to screen for cancer. Today, we’re going to help you understand what all of this means so you can better navigate the sea of information out there around cancer. So Dr. Klein, let’s start with genetic testing. What is genetic testing? How is it used in cancer care, and who is it for?
Dr. Klein 01:59
Genetic testing is a way of looking at the DNA that you were born with. So it’s things that you can blame your parents for. That’s the way I always look at it. And with respect to cancer, there are certain mutations in certain relatively small number of genes that we know predispose individuals for cancer and for specific kinds of cancer. And so the one that’s best known is a hereditary breast and ovarian cancer syndrome or the BRCA gene. And in individuals who are at increased risk based on this DNA testing, we generally apprise them of their risk and, and talk to them about being screened appropriately.
Kim Thiboldeaux 02:42
So let’s talk a little bit more about that Dr. Klein. When someone learns that they have a genetic mutation that puts them at a higher risk of cancer, say BRCA or perhaps other mutations, what should they do next?
Dr. Klein 02:54
Don’t panic. That’s always best.
Kim Thiboldeaux 02:58
Good advice. That’s a good first step.
Dr. Klein 03:00
Don’t panic. Go online and go to reliable sources, like the American Cancer Society website where you can read about these syndromes, or the National Cancer Institute website, and so forth. And then go talk to your doctor, talk to your primary care doctor, and understand what your risks are, how significant the risk is, because in reality, even though individuals born with these mutations are at higher risk for cancer, it’s not that everybody who has the mutation gets a cancer. But there are now well-defined screening protocols for those at high risk of getting cancer. And they’re done at regular intervals, depending upon which syndrome you might have. So you need to learn about that and either arrange with your primary care physician to get the right kind of screening or be referred to a high-risk clinic if you live near a major medical center, which often will have specialized services and social support systems for individuals like this. And one other piece of advice – reach out to others who have also inherited this mutation, because there are a wealth of support groups out there, and people who have been through what you think that you may be going through, and it’s always very helpful to know that someone else’s out there has been through it already, and they can help guide you.
Kim Thiboldeaux 04:19
Yeah, I think that’s great advice. Do some of the research, talk to your doctor, connect with others that might have the same that the same risk or mutation. There are a lot of advocacy groups, nonprofit organizations that can help with those connections. So I think all great advice, Dr. Klein. Let’s move on to cancer screening. So what are the most well-known methods of screening for cancer today?
Dr. Klein 04:41
There are five cancers that are endorsed by an organization called The US Preventive Services Taskforce, which makes recommendations about the risks and benefits of screening and only endorses those that have definite benefits. So the five that we screen for are colon cancer with colonoscopy or stool-based test; breast cancer with mammography or MRI; cervical cancer with Pap smears; lung cancer using low dose CT in individuals who are at high risk of lung cancer because of a smoking history; and then finally, prostate cancer with a PSA blood test.
Kim Thiboldeaux 05:25
And so just to clarify, these kinds of cancer screenings are different from the genetic testing that we were just discussing.
Dr. Klein 05:32
Yes, genetic testing, again, is a blood test to look at DNA that you were born with and what you might be at risk for. Cancer screens, these individual cancer screens are to determine if at this particular time in your life, are you, do you have this cancer? Or is there a suggestion that you might have this cancer that requires further workup? But they’re two different, they are definitely two different things.
Kim Thiboldeaux 05:59
And for these cancer screenings, these five screenings, there are different guidelines for who should be getting these screenings, when they should be getting these screenings, etc. So it’s important that our listeners educate themselves on that. We’re hearing also about a test called a called a liquid biopsy test for cancer. So what is a liquid biopsy? And does GRAIL’s Galleri test – is that a liquid biopsy?
Dr. Klein 06:25
Well, before we talk about that, let’s talk about the new paradigm of screening, which is multi-cancer detection. So, many companies are working in this space now. But it’s actually possible to take a blood sample and using very sophisticated ways of looking for DNA that is shed by cancers, to determine if there might be some cancer related DNA in your bloodstream, sort of a signal. And if that signal is present, then you go on to get a diagnostic workup. Just like you might for example, if you had an elevated PSA, if you were a man over 50, had an elevated PSA that doesn’t guarantee that you had prostate cancer. But it would dictate that your physician or urologist would do some other diagnostic tests. So multi-cancer early detection is really exciting because even though we screen for the five cancers that I mentioned, we still lose about 600,000 patients a year in the United States to cancer death. And the reason for that in large part is that the five screening tests that we have, which reduce mortality or the death rate from those cancers, don’t screen for 70% of the cancers that people get. So that’s the exciting part about multi-cancer early detection.
Kim Thiboldeaux 07:40
So let’s repeat that number, Dr. Klein. So you’re saying that the five screenings that we talked about (mammography, colonoscopy, etc.) that they only screen for about 30% of cancers. You’re saying 70% of cancers that we’re detecting in the US are cancers for which we do not have a current screening test?
Dr. Klein 08:01
That’s exactly correct.
Kim Thiboldeaux 08:03
>Okay, important statistics, and maybe a little bit eye opening –
Dr. Klein 08:08
Kim Thiboldeaux 08:09
-for our listeners. So it’s exciting to hear about some of the new technologies that are being brought forward. I also want to clarify, so let’s get back to this question of liquid biopsy, Dr. Klein. So what is liquid biopsy and is the Galleri test from GRAIL, is that a liquid biopsy?
Dr. Klein 08:27
Liquid biopsy is taking a body fluid, that could be blood or sputum or urine, and looking for a disease, it doesn’t necessarily have to be cancer. Liquid biopsy, it can be used for screening or potentially can be used for screening for other kinds of diseases. But the term liquid biopsy implies that there is a disease present. And so that’s not really, not really what Galleri’s test is about. Galleri is a screening test, like other screening tests, in the sense that it’s a screen for cancer. And what it detects is a cancer signal. So when cancer grows, and cells start turning over, and it starts to become invasive, it sheds cancer DNA into the bloodstream. And the nuts and bolts behind Galleri are that it’s possible to detect the presence of a cancer signal looking at that DNA. So it’s not really a liquid biopsy, even though it uses a blood test like liquid biopsies can.
Kim Thiboldeaux 09:30
Got it, got it, different technology. Okay, so Dr. Klein, genetic testing, just to remind our listeners tells us about our familial risk, family risk, like you said, blame the parents of getting cancer, in our lives, while cancer screenings, including MCED, which detects the cancer signal aims to tell us whether or not we have cancer already. Now, let’s go into this term genomic testing, sometimes referred to as biomarker testing or next generation sequencing. Where does that come into play when we’re talking about a cancer diagnosis?
Dr. Klein 10:05
Yeah, it’s also sometimes known as somatic genetic testing, just to confuse things a little more. So if you’re diagnosed with a cancer, and you have a tumor, it’s possible now to take a biopsy of that tumor or a blood test, and determine the sequence of the DNA and look at the mutations that are driving the cancer. And the way to think about that, the way I always explained it to patients is if you’re driving a car, you can go fast or slow. And, you know, depending upon how hard your foot is on the gas pedal. And the idea behind sequencing of known cancers is to look at how heavy that foot is, and specifically, what part of the foot is pushing on the, on the gas pedal so that you can determine prognosis. And more importantly, more and more now we can pick drugs that target the specific foot that’s pushing on the accelerator, and stop that from happening. So that’s what genomic testing or biomarker or somatic genomic testing is all about. That’s in individuals who have been diagnosed with a cancer and are looking for additional information on prognosis and treatment.
Kim Thiboldeaux 11:23
So that can give us information about my cancer, my tumor. Are there mutations, are there other unique things about my cancer that will then, as you say, maybe inform the decision-making process? So based on the results of those tests that will inform my medical team about what treatment I might respond best to. Am I saying that correctly?
Dr. Klein 11:46
Yeah, that’s correct. Yes.
Kim Thiboldeaux 11:48
So talk us through that a little bit more Dr. Klein.
Dr. Klein 11:50
So let me share a patient anecdote. This patient is someone that I know in Cleveland, and has gone public. And it goes back a number of years now, early in the precision medicine era. And I like to tell the story because it really illustrates dramatically what the potential is. So this gentleman was 22 years old. He lived in northwestern Ohio, and he was a medical student. And over a summer, he developed a cough, which he, like most young people, ignored for many months. Finally went to see his primary care physician and he had widespread metastatic lung cancer, even though he had never been a smoker. And he was so sick, he had so much fluid around his lungs that he very quickly ended up in the Cleveland Clinic ICU, where he was intubated and told multiple times, and his family were told multiple times that he was going to die. And so again, early in the Precision Medicine era, his tumor was biopsied and sequenced and turned out to have a mutation in a gene called ALK, “alk”, which is very well known in lung cancer now, but wasn’t known then. And remarkably, for him, the FDA had just approved a drug that targets ALK mutations, for a different disease, for leukemia. And so he was started on that drug. And within a couple of weeks, all the fluid that he had around his lungs resolved, and he was off the ventilator. And he walked out of the hospital, and he quit medical school, and he became a cancer researcher. And so that’s really a remarkable story that I think illustrates what the power of this technology is for sequencing, not only for genetic testing to determine your risk, but for cancer screening, using a test like Galleri all the way to, you know, genomic testing of a tumor and precision medicine, for treatment, and so forth. It really makes me excited about the whole field.
Kim Thiboldeaux 13:44
Well, that is an amazing story. And extraordinary and I think it is, I agree with you, so critical that there’s greater awareness of the importance of this genomic or biomarker testing and that patients are getting the appropriate testing in order to inform the treatment. I know this, the field of biomarker testing is continuing to evolve by the day, we’re discovering new tests and new mutations, and then are able to create these sort of companion diagnostics, and then treatments that go along, that go along with these with these tests. So I think it’s really exciting to hear about the science, Dr. Klein, and to hear, and maybe just in closing comments, we’re really, we’re really advancing the science of technology towards the full spectrum, right? So from early on, knowing folks who are at risk, maybe trying to detect cancer at earlier stages, and then those signals and then, you know, through to genomic testing and precision medicine. Can you just talk a little bit about that, are you, you know, I’m sort of excited about that, that continuum of care. I’m sure you are too as a doctor and scientist.
Dr. Klein 14:43
So let me put it in perspective. I am very excited by it. And I’ll put it in perspective over the course of my career. When I was a fellow at Sloan Kettering, I chose to work in truly a genetics lab then, this was before sequencing was available. And I spent at my time, then growing tumors in tissue culture and harvesting their chromosomes and taking pictures of their chromosomes, and then literally using scissors and photographic paper and cutting out all the chromosomes and lining them up the way you see what’s called a karyotype, to 23 chromosomes. And we bought one of the very first machines that ultimately was kind of the backbone for molecular biology called an RT PCR machine that cost $5,000. First generation, it was huge, took up the whole desk. And we’ve seen our ability to get all that information and more with sequencing of DNA go from several hundred million dollars, down now to about $200 to sequence an entire human genome. And that’s just incredibly powerful. The amount of information that we’re able to generate from doing that now and the way that affects patients’ lives in a positive way is really inspiring.
Kim Thiboldeaux 15:57
I agree, inspiring. It’s so great to talk with you today Dr. Klein about the promise of, of this science and technology. So I appreciate you joining us for the conversation. This is The Cancer SIGNAL presented by GRAIL. I’m Kim Thiboldeaux. Please rate our podcast or leave a review and subscribe to learn more about the impact of early cancer detection on future episodes. Thank you.
Important Safety Information
The Galleri test is recommended for use in adults with an elevated risk for cancer, such a those aged 50 or older. The Galleri test does not detect all cancers and should be used in addition to routine cancer screening tests recommended by a healthcare provider. Galleri is intended to detect cancer signals and predict where in the body the cancer signal is located. Use of Galleri is not recommended in individuals who are pregnant, 21 years old or younger, or undergoing active cancer treatment.
Results should be interpreted by a healthcare provider in the context of medical history, clinical signs and symptoms. A test result of “No Cancer Signal Detected” does not rule out cancer. A test result of “Cancer Signal Detected” requires confirmatory diagnostic evaluation by medically established procedures (e.g. imaging) to confirm cancer.
If cancer is not confirmed with further testing, it could mean that cancer is not present or testing was insufficient to detect cancer, including due to the cancer being located in a different part of the body. False-positive (a cancer signal detected when cancer is not present) and false-negative (a cancer signal not detected when cancer is present) test results do occur. Rx only.
GRAIL’s clinical laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by the College of American Pathologists. GRAIL’s clinical laboratory is regulated under CLIA to perform high-complexity testing. The RUO test was developed, and its performance characteristics were determined by GRAIL. The RUO test is For Research Use Only, Not for Diagnostic Purposes. GRAIL’s current product offerings have not been cleared or approved by the Food and Drug Administration.